Wikipedia

Cluster of Excellence Frankfurt Macromolecular Complexes

The Cluster of Excellence Frankfurt "Macromolecular Complexes" (CEF) was established in 2006 by Goethe University Frankfurt together with the Max Planck Institute of Biophysics and the Max Planck Institute for Brain Research in the context of the German Universities Excellence Initiative. Funding by the Deutsche Forschungsgemeinschaft (DFG) endet in October 2019. CEF grew out of the long-standing collaborative research on membrane proteins and RNA molecules and strengthened research efforts in these fields by recruiting further scientists to Frankfurt/Main. CEF brought together the research activities of up to 45 research groups, the majority of which were based on Riedberg Campus in Frankfurt/Main. CEF founded the Buchmann Institute for Molecular Life Sciences (BMLS).

Aims edit

CEF scientists set out to investigate the structure and function of large macromolecular complexes, in particular membrane proteins and their assemblies, complexes involved in signal transduction and quality control, and RNA-protein complexes.

Research edit

Important structures of macromolecular complexes were determined in CEF. Examples for important membrane complexes include the atomic structures of complex I and the ATP synthase of the mitochondrial respiratory chain and of the transporter associated with antigen processing (TAP). Research on RNA structure and function led to the definition of regulatory principles of temperature sensing riboswitches, the structure-function relationship of RNA polymerase I, the functions of microRNAs and the mechanisms of rRNA maturation and downstream processes during ribosome biogenesis and recycling. For instance, CEF scientists identified the receptors of ubiquitin chains on the proteasome, deciphered the role of linear ubiquitin chains and described macromolecules regulating mitophagy, xenophagy and ER-phagy. They delineated the role of sumoylation in ribosome quality control and characterized the process of genetic quality control in oocytes. The efforts in these three research areas were accompanied by approaches to design or reprogram macromolecular complexes and new methods developed to expand the already strong expertise. CEF scientists established and advanced the principles of optogenetics as well as biochemical methods for light regulation. They also developed biophysical techniques for the structural and functional characterization of macromolecules. Example include light-switchable molecules designed for in-cell applications and time-resolved techniques to study RNA folding. Light sheet fluorescence microscopy for the observation of development and LILBID mass spectrometry for the analysis of membrane complexes was improved. PELDOR-EPR was developed to a resolution that allows in-cell measurements. The Cluster promoted scientific exchange through a range of programmes as well as through workshops, international conferences and lecture series. Optogenetics and light sheet fluorescence microscopy were selected as the "Method of the Year" across all fields of science and engineering by the interdisciplinary research journal Nature Methods in 2010 and 2014, respectively.[1][2]

The five research areas of CEF included: (A) Structure, mechanisms and dynamics of complexes in the membrane, (B) Composition and dynamics of macromolecular complexes in quality control and signalling, (C) Dynamics of ribonucleic acid-protein-complexes, (D) Design of macromolecular complexes, and (E) Methods for studying macromolecular complexes.

CEF Research Area A - Structure, mechanisms and dynamics of complexes in the membrane edit

Biological membranes have a very important role in life processes as everything a cell needs to live, grow and respond has to either pass through or act on them. The energy conversion processes of cellular respiration and photosynthesis happen in membranes, every sensory stimulus and the information processing in the brain is mediated by them. This array of diverse actions is performed by a large number of different membrane proteins. In the crowded conditions of the cell membrane, most membrane proteins associate into complex dynamic assemblies to carry out their various tasks. For this reason, and because they are embedded in the lipid bilayer of the membrane, most membrane proteins are difficult to study and their functions have often been intractable. CEF scientists have done groundbreaking work to overcome some of these challenges and made major contributions to elucidating the structure, mechanisms and regulation of a number of important large complexes, including respiratory complex I,[3][4] rotary ATPases,[5][6][7][8] supercomplex I1III2IV1,[9][10] cytochrome cbb3 oxidase,[11] cytochrome bd oxidase,[12] a sulfide:quinone oxidoreductase,[13] a fungal TOM core complex,[14] a bacterial double-pore K+ uptake system KtrAB,[15] the Na+-independent carnitine/butyrobetaine antiporter CaiT,[16] the betaine/Na+ symporter BetP,[17] the multidrug efflux transporter AcrB[18][19] and the chaperone and editing TAPBPR–MHC I complex[20] and the human MHC-I peptide-loading complex.[21] Antigenic peptide recognition on TAP was resolved by DNP-enhanced solid-state NMR spectroscopy.[22] The conformational coupling and trans-inhibition in the human antigen transporter ortholog TmrAB was resolved with the aid of dipolar EPR spectroscopy.[23] The progress in 3D structure determination of membrane proteins by X-ray crystallography and cryo electron microscopy has created an increasing demand and opportunity for in-depth mechanistic studies by magnetic resonance methods. Due to the challenges intrinsic to membrane proteins, progress relies on the availability of techniques at the forefront of method development. Especially solid-state (MAS) NMR enables bridging the gap between 'static' structures and biochemical data by probing membrane proteins directly within the bilayer environment. Such experiments are challenging and breakthroughs could only be achieved thanks to the availability of dynamic nuclear polarization for sensitivity enhancement and very high magnetic fields for spectral resolution. CEF scientists were able to provide new insights into the catalytic mechanism of ABC transporters. Based on real-time 31P-MAS-NMR they found that the homodimeric lipid A flippase MsbA is able to catalyze a reverse adenylate kinase-like reaction in addition to ATP hydrolysis.[24] In addition, the ATP hydrolysis cycle of the ABC transporter LmrA was probed by site-directed spin labeling and pulsed electron–electron double resonance (PELDOR/DEER) spectroscopy.[25] The secondary multidrug efflux pump EmrE from E. coli was extensively studied with 31P- and DNP-enhanced solid-state NMR.[26] Also, a number of photoreceptors such as microbial rhodopsins are involved in trans-membrane transport processes. For example, fundamental contributions were made towards the structural and functional description of proteorhodopsin, a pentameric light-driven proton pump by groups within CEF.[27][28][29] CEF researchers have developed mass spectrometry approaches specifically suitable for large membrane protein complexes. Laser induced liquid beam/bead ion desorption mass spectrometry (LILBID) enables mass analysis of whole membrane protein complexes of 1 MDa or more.[30] A team of CEF scientists resolved the mechanism of the subtype selectivity of human bradykinin receptors for their peptide agonists by integrating DNP-enhanced solid-state nuclear magnetic resonance with advanced molecular modeling and docking[31]

CEF Research Area B - Composition and dynamics of macromolecular complexes in quality control and signalling edit

The characterization of function and structural composition of signalling complexes controlling cellular quality control programs was one of the major topics of CEF research. The view that proteins act as single entities has been replaced with the concept suggesting that dynamic reorganization of multimeric soluble complexes annotated as signalosomes is essential for signal transmission in the cell. Regulation of the activity of these complexes is achieved by their dynamic composition as well as by post-translational modifications (PTMs) of proteins. Domains that recognize these modifications play decisive roles in a cell's ability to respond to alterations in their microenvironment. Significant progress has been accomplished by CEF in characterizing several signalling pathways and their regulation by PTMs including ubiquitylation, phosphorylation and acetylation. A particular focus of research in CEF has been on protein quality control mechanisms that are the basis for the autophagic and the ubiquitin/proteasomal pathways, the two cellular systems used to degrade faulty or superfluous proteins, complexes and organelles. Additional foci of CEF research were genetic quality control in oocytes and epithelial stem cells by the p53 protein and the regulation of and by kinases.

Research into autophagy edit

During selective autophagy, cargo is specifically targeted for degradation, and distinct cargo receptors have been described that regulate selectivity. This process is facilitated by autophagy receptors specifically recognizing and binding their cargo, and delivering it to the phagophore. In humans, there are six different LC3/GABARAP proteins, which play a central role by connecting nascent autophagosome membranes and cargo-loaded autophagy receptors to facilitate engulfment, sometimes mediated or supported by additional adaptor proteins.[32] CEF scientists showed that GABARAP proteins are not only involved in autophagy but also in the ubiquitin-dependent degradation of TIAM1.[33] Breakthroughs were achieved in how cells fight intracellular pathogens and how intracellular bacteria try to evade these counter measures. The kinase Tbk1 was identified as important for mediating optineurin based xenophagy to remove the bacteria from the infected cells.[34] Using mass spectrometry, a global analysis of the ubiquitinome of Salmonella-infected cells was carried out, that enabled CEF scientists to identify specific targets of bacterial ligases that are secreted into the cellular cytoplasm by the pathogens.[35] CEF scientists also revealed the molecular mechanism of a novel type of phosphoribosyl-linked serine ubiquitination by the effector SdeA of the pathogen Legionella, which is very different from the canonical lysine-based ubiquitination mechanism.[36][37] They further showed that another effector of Legionella bacteria, SidJ, opposes the toxicity of SidE in yeast and mammalian cells.[38] Mass spectrometry analysis revealed that SidJ is a glutamylase that modifies the catalytic glutamate in the mono-ADP ribosyl transferase domain of the SdeA, thus blocking the ubiquitin ligase activity of SdeA. They further discovered that reticulon-type proteins act as ER-specific autophagy receptors and simulated their effect on the membrane curvature.[39][40]

Ubiquitination edit

Ubiquitination plays a central role for marking proteins to be degraded either via the autophagy pathway or via the proteasome. Several groups of CEF have contributed to advances in understanding how ubiquitin signalling is not only used as a degradation signal but also involved in several other cellular processes[41][42][43][44][45][46]

p63 edit

Research on TP63, also known as p63, has shown that this protein plays essential roles both for the proliferation and differentiation of stratified epithelial tissues as well as for the surveillance of the genetic quality in female germ cells. Investigations by CEF scientists showed that a specific isoform of p63 is highly expressed in primordial oocytes which are arrested in prophase of meiosis I. This isoform adopts a closed, inactive and only dimeric conformation in which both, the interaction with the DNA as well as with the transcriptional machinery is significantly reduced[47] The inhibition is achieved by blocking the tetramerization interface of the oligomerization domain with a six-stranded anti-parallel beta-sheet.[48] Activation requires phosphorylation and follows a spring-loaded, irreversible activation mechanism.[49] These discoveries open the possibility to develop a therapy for preserving oocytes during chemotherapy which in female cancer patients usually results in infertility and the premature onset of menopause. CEF scientists also helped to identify the molecular mechanism causing ankyloblepharon-ectodermal dysplasia-cleft lip/palate syndrome, a disease characterized by skin erosions, oral clefting abnormalities and fused eyelids, which is based on mutations in the SAM domain or in the C-terminus of p63.[50] Complexes involved in tumorigenesis were studied by several CEF groups, including the leukemogenic AF4-MLL fusion protein[51] and RIP1-containing cytosolic complexes that are critical for the initiation and fine-tuning of different forms of cell death, i.e. apoptosis and necroptosis[52][53]

SGC Frankfurt edit

Goethe University became a member of the Structural Genomics Consortium (SGC) in 2017, an international consortium and public-private partnership dedicated to the determination of structures of important proteins and the development of inhibitors and probes for biological macromolecules to be used in functional investigations. Goethe University has also become the home and reference center for the SGC's donated probes programme, that makes small molecules no longer being further pursued by industry as drug targets freely available to researchers worldwide[54]). CEF scientists have developed bromodomain inhibitors that can be used to study the function of these acetyl-lysine modification binding domains. A set of probes has been characterized and validated as tools for specific bromodomains[55]

Interactions with soluble domains at the membrane edit

CEF showed that vascular endothelial growth factor receptor-2 needs to be internalized and is regulated by its association to ephrin B2 in endothelial cells.[56] Ephrin B2 was also found to be essential to control levels of AMPA receptors at the synaptic membrane.[57] The mechanism of membrane insertion of tail-anchored proteins was studied by structural and biochemical characterization of the interaction of the soluble Get3 protein with the cytoplasmatic domains of the membrane-bound receptors Get1 and Get2.[58]

CEF Research Area C - Dynamics of ribonucleic acid-protein-complexes edit

Many discoveries including the identification of multiple classes of noncoding RNAs and regulatory RNA elements has broadened the perspective on RNA function from a passive carrier of information to an active cellular component. Its structural and functional description is required to understand the molecular interactions and the dynamics involved.

Structural description of RNA elements and their dynamics edit

The combination of high-resolution NMR-based analysis of RNA structures[59][60] and time-resolved ligand-induced refolding of RNAs by caging distinct conformations[61] together with pulsed electron paramagnetic resonance methods (PELDOR) after base-specific spin-labeling[62][63][64] and ultrafast laser spectroscopy of RNA dynamics[65][66] has led to the description of the structural dynamics of several RNAs. CEF scientists showed that the regulation mechanism of the adenine-sensing riboswitch of the human pathogenic bacterium Vibrio vulnificus is notably different from a two-state switch mechanism in that it involves three distinct stable conformations. This translational adenine-sensing riboswitch represented the first example of a temperature-compensated regulatory RNA element .[67] The composition and structure of the HIV TAR RNA-Ligand complex was analyzed by LILBID and NMR,[68][69] leading to a description of the complexity of peptide binding sites in RNAs. Furthermore, the guanine-sensing riboswitch-aptamer domain of the Bacillus subtilis xpt-pbuX operon, the Diels-Alderase ribozymes[70] an RNA-based thermometer,[71] and the N1–ribostamycin complex[72] were structurally and functionally analyzed. CEF scientists also showed that for the guanine-sensing xpt-pbuX riboswitch of B. subtilis, the conformation of the full-length transcripts is static: it exclusively populates the functional off-state but cannot switch to the on-state, regardless of the presence or absence of ligand. Only the combined matching of transcription rates and ligand binding enables transcription intermediates to undergo ligand-dependent conformational refolding[73](Steinert et al., 2017).

Components involved in ribosome biogenesis in eukaryotes edit

CEF scientists in collaboration with the Max Planck Institute for Biophysical Chemistry visualized the RNA Polymerase I (Pol I) in the process of actively transcribing ribosome genes in a cellular environment and solved its structure with and without nucleic acids at 3.8 Å resolution by cryo-EM.[74] Their structures explained the regulation of transcription elongation in which contracted and expanded polymerase conformations are associated with active and inactive states, respectively.

Work by a collaboration between several CEF groups unravelled the molecular nature of Bowen-Conradi syndrome by demonstrating that the disease-causing point mutation of the ribosome biogenesis factor Nep1 impairs its nucleolar localisation and RNA binding.[75][76] Another study, in collaboration with Edinburg University, analysed the RNA helicase Prp43 by crosslinking of RNA and analysis of cDNA (CRAC) and provided first insights into the functional roles of this enzyme in ribosome biogenesis[77] CEF scientists also identified plant-specific ribosome biogenesis factors in A. thaliana with essential function in rRNA processing[78] and showed that the 60S-associated ribosome biogenesis factor LSG1-2 is required for 40S maturation in A. thaliana.[79]

Distribution of RNA-modifying enzymes and RNA molecules edit

The dynamics of RNPs in native environments in eukaryotic cells were visualized and quantified using high-resolution microscopy.[80] Adenosine-to-inosine (A-to-I) RNA editing, which is catalyzed by adenosine deaminase acting on RNA (ADAR) enzymes, is important in the epitranscriptomic regulation of RNA metabolism. Cathepsin S (CTSS) mRNA, which encodes a cysteine protease associated with angiogenesis and atherosclerosis, was shown to be highly edited in human endothelial cells .[81] A-to-I RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation.

mRNA export from the nucleus to the cytoplasm is a highly regulated step in gene expression. CEF scientists evaluated members of the SR protein family (SRSF1–7) for their potential to act as adaptors for nuclear export factor 1 (NXF1) and thereby couple pre-mRNA processing to mRNA export.[82] They found that >1000 endogenous mRNAs required individual SR proteins for nuclear export in vivo. To address the mechanism, transcriptome-wide RNA-binding profiles of NXF1 and SRSF1–7 were determined in parallel by individual-nucleotide-resolution UV crosslinking and immunoprecipitation (iCLIP). SRSF3 emerged as the most potent NXF1 adaptor, conferring sequence specificity to RNA binding by NXF1 in last exons. Numerous human diseases are characterised by a widespread dysregulation of RNA-binding proteins (RBPs) and massively altered transcriptome patterns. CEF scientists used computational methods to study the mechanisms of posttranscriptional regulation on a transcriptomic scale, in collaboration with researchers at IMB Mainz.[83]

Noncoding RNAs edit

CEF scientists also investigated the influence of novel |noncoding RNAs]], such as long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), on cellular function. miRNAs regulate gene expression by binding to target mRNAs and preventing their translation. One of the CEF Focus Projects succeeded in observing the activity-dependent spatially-localized miRNA maturation in neuronal dendrites.[84] Local maturation of the miRNA was found to be associated with a local reduction in protein synthesis, showing that localized miRNA maturation can modulate target gene expression with local and temporal precision. LncRNA Meg3 was found to control endothelial cell aging and its inhibition may serve as a potential therapeutic strategy to rescue aging-mediated impairment of endothelial cell function.[85] LncRNA MALAT1 was found to regulate endothelial cell function and vessel growth.[86] and protects against atherosclerosis by regulating inflammation.[87]

CEF Research Area D - Design of macromolecular complexes edit

A major focus of work in CEF was to develop and use methods and to explore proteins that enable modulating cellular and molecular function with light. In the field of optogenetics, control of membrane potential and intracellular signalling in neurons and other cells is achieved by expression of photosensor proteins, in most cases of microbial origin, e.g. ion channels or pumps, as well as light-activated enzymes. Optochemical approaches, in contrast, use chemically engineered molecules to achieve light-effects in biological tissue.

Optogenetics edit

The origin of optogenetics lies in the work of the Bamberg group at the MPI of Biophysics in Frankfurt, who showed that channelrhodopsin-2 (ChR2) is a light-gated cation channel that can depolarize the cells in which it is expressed.[88][89] During CEF, the Bamberg lab continued to work in this field and contributed several seminal papers, e.g. on the characterization[90][91][92] but also on the engineering of ChR2 to optogenetic tools with different properties.[93] The first utilization of ChR2 for depolarization of mammalian cells and generation of the first ChR2-transgenic animal took place in Frankfurt. The Gottschalk lab introduced ChR2, the light-driven Cl—pump halorhodopsin and other rhodopsins into the nervous system of the nematode C. elegans, to stimulate single neurons and correlate their function with a behavioural output.[94][95][96] In addition, they studied synaptic transmission after photostimulation, using ChR2 and a photoactivated adenylyl cyclase (PAC), in combination with electrophysiology and electron microscopy,[97][98] and introduced modified or novel optogenetic tools with altered properties, for blocking synaptic transmission, or for the manipulation of cyclic GMP.[99][100][101] Several CEF groups joined forces not only to unravel the photocycle of ChR2 at different time scales[102] but also provided, in collaboration with the Research Centre Juelich, structural insights into ion conduction by ChR2.[103] They also generated several mutant ChR2 versions with altered ion conductance (for example increased Ca2+-permeability in "CatCh", a Ca2+ transporting channelrhodopsin) or kinetics, representing highly useful additions to the optogenetic toolbox .[104] In 2015, CEF scientists presented the first NMR study which resolved structural details of the retinal cofactor of ChR2. This study was only possible because DNP (a hybrid method linking EPR with solid-state NMR spectroscopy) enhanced the detection sensitivity 60-fold so that metastable intermediates could be detected. In this way, first unambiguous evidence was provided for an exclusive all-trans retinal conformation in the dark state and a new photointermediate could be identified. The study showed that DNP-enhanced solid-state NMR is a key method for bridging the gap between X-ray–based structure analysis and functional studies towards a highly resolved molecular picture .[105]

It gradually emerged that rhodopsins have a wide spectrum of functions and distribution and are found in all phyla of life. With the new rhodopsins came the observation that they represent a rather versatile family of proteins while retaining the structural scaffold of seven transmembrane helices with a retinal chromophore bound to a conserved lysine.[106] CEF scientists have studied the structure as well as the function of microbial rhodopsins. One of these is proteorhodopsin, found in marine microbes, which is the most abundant retinal-based photoreceptor on our planet. Variants of proteorhodopsins show high levels of environmental adaptation, as their colours are tuned to the optimal wavelength of available light.[107][108][109][110][111]

CEF scientists together with colleagues from other German universities developed a novel approach to alter the functional properties of rhodopsin optogenetic tools, namely by modifications of the retinal chromophore. Synthetic retinal analogs were introduced into ChR2 or other rhodopsin tools in C. elegans, Drosophila and human cells, to change the light sensitivity, photo cycle kinetics and colour spectrum of the optogenetic actuators.[112] They also established the tightly light-regulated guanylyl-cyclase opsin CyclOp that enabled rapid light-triggered cGMP increase.[113] CEF scientists have also used optogenetic tools for the analysis of neural circuits and how they drive behaviour.[114][115][116]

Optochemical approaches edit

To control proteins and nucleic acids by light CEF scientists have designed and applied a range of photoswitchable tethers, ribonucleosides and nucleic acids, RNA aptamers and "beacons".[117][118][119][120][121] They also developed an approach for the chemo‐enzymatic synthesis of position‐specifically modified RNA for biophysical studies including light control.[122] Furthermore, light-activatable interaction of DNA nanoarchitectures, light-dependent conformational changes in nucleic acids, light-dependent RNA interference and light-dependent transcription were realized.[123][124] Wavelength-selective light-triggering was established for nucleic acids[125] as well as three-dimensional control of DNA hybridization by orthogonal two-colour two-photon uncaging.[126] CEF scientists developed a red-shifted two-photon-only caging group for three-dimensional photorelease.[127] They also developed a minimal light‐switchable module enabling the formation of an intermolecular and conformationally well‐defined DNA G‐quadruplex structure with a photoswitchable azobenzene residue as part of the backbone structure.[128] Important was also the development of an inducible fluorescent probe which enabled the detection of activity-dependent spatially localized miRNA maturation in neuronal dendrites.[129] Using light-inducible antimiRs, CEF scientists also investigated if locally restricted target miRNA activity has a therapeutic benefit in diabetic wound healing and found that light can be used to locally activate therapeutically active antimiRs in vivo.[130]

New building principles for DNA-nanoarchitectures have been established in CEF[131][132][133] Also, new RNA riboswitches have been designed that can be triggered with small metabolites, exogenous molecules, or by temperature changes, as well as aptamers or self-cleaving ribozymes, which can be used to control gene expression in vivo.[134] Making macromolecules further accessible on the nano-scale for manipulation, CEF developed generally applicable methods to organize macromolecular complexes in two dimensions with very high precision, as well as small synthetic gatekeepers and novel "light switches" to control biomolecular interactions and assembly of macromolecular complexes[135][136][137][138][139] An approach to assemble three-dimensional protein networks by two-photon activation was developed.[140] CEF scientists also achieved optical control of antigen translocation using synthetic photo-conditional viral inhibitors.[141]

Protein engineering edit

CEF scientists used detailed structural knowledge of the fatty acid synthase (FAS) megacomplex to engineer FAS for the biosynthesis of short-chain fatty acids and polyketides, guided by a combined in vitro and in silico approach .[142] They reprogrammed chain-length control of the FAS of Saccharomyces cerevisiae to create a baker's yeast able to produce short-chain fatty acids. A rational and minimally invasive protein engineering approach was used that left the molecular mechanisms of FASs unchanged and identified five mutations that can make baker's yeast produce short-chain fatty acids.[143] To manipulate a protein photocycle in a directed manner, CEF groups collaborated to modify the flavoprotein dodecin at its key amino acid tryptophan with substituents carefully selected for their structural and electronic influence.[144]

CEF Research Area E - Methods for studying macromolecular complexes edit

The development of cutting-edge methodologies, including electron paramagnetic resonance (EPR), time-resolved nuclear magnetic resonance spectroscopy (NMR), advanced fluorescence microscopy, as well as optogenetics and optochemical biology has been instrumental in the research efforts of CEF. The Cluster also integrated new developments in electron microscopy and tomography as well as in super-resolution microscopy into the methods portfolio of Riedberg Campus.

Cryo-electron microscopy edit

Cryo-electron microscopy, Nature Method of the Year 2015[145] and the method for which a Nobel prize was awarded in 2017,[146] was extensively employed by several CEF groups, at the MPI of Biophysics as well as at Goethe University's Buchmann Institute for Molecular Biology.[147][148][149][150][151] Direct electron detectors, in the development of which the MPI of Biophysics was involved, have exceeded all expectations[152][153] With these detectors, images can be captured with much higher contrast than with the CCD cameras previously used and have led to amazing progress in structural biology. By investing in this new technology, CEF members have been able to speed up structure determination and also solve the structures of macromolecular complexes that were not amenable to x-ray crystallography studies. Another focus of CEFs electron microscopists was to reveal the macromolecular organisation of living cells by means of cryo-electron tomography. Cryo-ET is the only technique that can obtain molecular resolution images of intact cells in a quasi-native environment. Such tomograms contain a large amount of information as they are essentially a three-dimensional map of the cellular proteome and depict the whole network of macromolecular interactions. Information-mining algorithms exploit structural data from various techniques, identify distinct macromolecules and computationally fit atomic resolution structures in the cellular tomograms, thereby bridging the resolution gap.[154]

Light microscopy edit

The Cluster also strongly support new developments in advanced light microscopy. A particularly important technique CEF added to the research technique portfolio in Frankfurt is light sheet fluorescence microscopy (LSFM)[155][156]). In LSFM, optical sectioning in the excitation process minimizes fluorophore bleaching and phototoxic effects. Because with LSFM biological specimens survive long-term three-dimensional imaging at high spatiotemporal resolution, such microscopes have become the tool of choice in developmental biology. The impact of LSFM was recognized in 2015, when the journal Nature Methods elected it as the "Method of the Year 2014".[157] CEF scientists used LSFM, for example, to image in detail the complete embryonic development of different evolutionary unrelated insects and to establish the rules and self-organizing properties of post-embryonic plant organ cell division patterns.[158][159][160] The large amount of data produced by advanced light microscopy has made automated image analysis a necessity and CEF has contributed to improved data processing and modelling of advanced light microscopy data.[161][162] Other novel light microscopy techniques used by CEF scientists include techniques that provide single-molecule sensitivity and a spatial resolution below the diffraction limit to study the structural organization of biomolecules in cells. Software tools developed by CEF scientists include for example SuReSim, a software developed in collaboration with Heidelberg University, that simulates localization data of arbitrary three-dimensional structures represented by ground truth models, allowing users to systematically explore how changing experimental parameters can affect potential imaging outcomes.[163] Using the newly developed techniques, CEF scientists were able to establish the role of the linear ubiquitin coat around the cytosolic pathogen Salmonella Typhimurium as the local NF-κB signalling platform and provided insights into the function of OTULIN in NF-κB activation during bacterial pathogenesis.[164] Another example is the identification of reticulon 3 (RTN3) as a specific receptor for the degradation of ER tubules.[165] The close collaborative teamwork of the consortium allowed tackling two major challenges in live-cell as well as single-molecule localization microscopy: efficient delivery of fluorophores across cell membranes and high-density protein tracing by ultra small labels.[166][167] Collectively, the new tools provide additional avenues to specifically manipulate and trap cellular proteins, and, at the same time, for high-resolution read-out by single-molecule based microscopy.

Spectroscopy methods edit

A wide range of spectroscopy methods for biological applications were available within CEF and CEF scientists have made significant progress in further developing biomolecular NMR and EPR. The members of the Center for Biomolecular Magnetic Resonance (BMRZ) improved the sensitivity of liquid- and solid-state NMR by a spectrometer featuring dynamic nuclear polarization (DNP). Together with researchers from the Russian Academy of Sciences, CEF scientists developed a high-power gyrotron source for DNP. The source operates at 260 GHz with an output power of 20 W, and is connected by a quasi-optical corrugated waveguide to one liquid- and one solid-state 400 MHz NMR spectrometer. The microwave board, which detects the EPR signal and connects the high-power microwave source to the NMR probe, was constructed in collaboration with scientists from the Ukrainian Academy of Sciences. This unique device is based on a metallo-dielectric waveguide system, which guarantees ultra-low losses combined with a high degree of flexibility in terms of instrument design. CEF's scientists demonstrated a proton NMR signal enhancement in aqueous liquids by up to 80-fold at magnetic fields of 9. T,[168] thus exceeding theoretical predictions by more than a factor of 20. First applications to macromolecular complexes have been equally successful. They also recorded signal enhancements by a factor up to 40 under magic angle sample spinning (MAS) conditions at 100 K with proteorhodopsin re-constituted into lipid bilayers. By integrating DNP-enhanced solid-state NMR spectroscopy with advanced molecular modeling and docking, the mechanism of the subtype selectivity of human kinin G-protein-coupled receptors for their peptide agonists was resolved.[169] DNP-enhanced solid-state NMR spectroscopy enabled CEF scientists to determine the atomic-resolution backbone conformation of an antigenic peptide bound to the human ABC transporter TAP. Their NMR data also provided unparalleled insights into the nature of the interactions between the side chains of the antigen peptide and TAP. Their findings revealed a structural and chemical basis of substrate selection rules, which define the crucial function of this ABC transporter in human immunity and health. This work was the first NMR study of a eukaryotic transporter protein complex and demonstrated the power of solid-state NMR in this field[170] They also demonstrated the power of DNP-enhanced solid-state NMR to bridge the gap between functional and structural data and models.[171] In parallel to the DNP developments, a pulsed electron–electron double resonance (PELDOR) spectrometer with a magnetic field of 6.4 T was constructed. A protein concentration of only 10 pMol is sufficient for a measurement at 40 K. With this instrument, CEF scientists were able to determine the dimeric structure of non-covalent protein complexes. This method is also applicable to membrane proteins and spin-labelled RNA and DNA molecules in vivo.[172] PELDOR spectroscopy proved to be a versatile tool for structural investigations of proteins, even in the cellular environment. In order to investigate for example the structural implications of the asymmetric nucleotide-binding domains and the trans-inhibition mechanism in TAP orthologs, spin-label pairs were introduced via double cysteine mutants at the nucleotide-binding domains and transmembrane domains in TmrAB (a functional homologue of the human antigen translocation complex TAP) and the conformational changes and the equilibrium populations followed using PELDOR spectroscopy.[173] This study defined the mechanistic basis for trans-inhibition, which operates by a reverse transition from the outward-facing state through an occluded conformation. The results uncovered the central role of reversible conformational equilibrium in the function and regulation of an ABC exporter and established a mechanistic framework for future investigations on other medically important transporters with imprinted asymmetry. The study also demonstrated for the first-time the feasibility to resolve equilibrium populations at multiple domains and their interdependence for global conformational changes in a large membrane protein complex.

Mass spectrometry edit

Native mass spectrometry has emerged as an important tool in structural biology. Advantages of mass spectrometry compared to other methods like X-ray crystallography or nuclear magnetic resonance are for instance its lower limits of detection, its speed and its capability to deal with heterogeneous samples. CEF contributed to the development of laser-induced liquid bead ion desorption mass spectrometry (LILBID), a method developed at Goethe University that is especially suited to the analysis of large membrane protein complexes.[174] A challenge in native mass spectrometry is maintaining the features of the proteins of interest, such as oligomeric state, bound ligands, or the conformation of the protein complex, during the transfer from the solution to the gas phase. This is an essential prerequisite to allow conclusions about the solution state protein complex, based on the gas phase measurements. Therefore, soft ionization techniques are required. While standard methods, such as nESI and matrix-assisted laser desorption/ionization (MALDI) reliably deliver valuable results for soluble proteins, they are not universally applicable to the more challenging matrices which are often required for membrane protein complexes. Generally an artificial membrane mimetic environment is required to maintain a membrane protein complex in its native state outside of the cellular environment.[175][176] With LILBID the analyte is transferred into the mass spectrometer in small droplets (30 or 50 µm diameter) of the sample solution produced by a piezo-driven droplet generator and is desorbed from the aqueous solution by irradiation with a mid-IR laser. This results in biomolecular ions with lower, more native-like charge states in comparison to nESI. At ultra-soft desorption conditions, even weakly interacting subunits of large protein complexes remain associated, so that the mass of the whole complex can be determined. At higher laser intensities, the complex dissociates by thermolysis and subunit masses are recorded. A broad range of macromolecular complexes from CEF research areas A, C and D, including complex I, ATP synthase, drug transporters with binding proteins, ion channels, proteorhodopsins and DNA/RNA complexes, have been analysed using LILBID.[177][178][179][180]

Time-resolved spectroscopy edit

Femtosecond time-resolved spectroscopy was used by CEF scientists to study molecular dynamics and function. This method enables the observation of extremely fast chemical and biological reactions in real time involving a wide variety of molecules from small organic compounds to complex enzymes. Studies included molecular systems like optical switches, natural and non-natural photosynthetic model systems and membrane protein complexes. Fundamental processes in molecular physical chemistry were investigated, such as photoisomerization, energy and electron transfer and reaction dynamics at surfaces. Modern methods in quantum optics for the generation of appropriately shaped and tunable femtosecond pulses in the visible and infrared spectral range were employed and further developed. Examples of these studies include the investigation and deciphering of the dynamics of photoswitchable or photolabile compounds as basis for the design of photoresponsive biomacromolecules, of the primary reaction dynamics of channelrhodopsin-2 (ChR2) and of the conformational dynamics of antibiotic-binding aptamers: Photochromic spiropyrans are organic molecules that can be used for the triggering of biological reactions.[181][182][183][184][185]

Theoretical biophysics and bioinformatics edit

Method development in theoretical biophysics plays an increasingly important role in the study of macromolecular complexes and has made essential contributions to many studies in the other research areas of CEF. Bridging between fundamental physics, chemistry and biology, CEF scientists studied biomolecular processes over a broad resolution range, from quantum mechanics to chemical kinetics, from atomistic descriptions of physical processes and chemical reactions in molecular dynamics (MD) simulations to highly coarse-grained models of the non-equilibrium operation of molecular machines and network descriptions of protein interactions. Their goal is to develop detailed and quantitative descriptions of key biomolecular processes, including energy conversion, molecular transport, signal transduction, and enzymatic catalysis. Within CEF, they worked in close collaboration with experimental scientists who employ a wide variety of methods. Their computational and theoretical studies aided in the interpretation of increasingly complex measurements, and guided the design of future experiments.[186][187][188][189][190] The interdisciplinary field of bioinformatics opened new perspectives on molecular processes and cellular function. CEF scientists used custom-tailored code and pipelines for fast and efficient analysis[191] of omics data, with a primary focus on protein-RNA interactions and posttranscriptional regulation.[192][193][194] They also develops algorithms to solve problems in molecular biology, ranging from atomic protein structure analysis to computational systems biology. Their tools leverage on graph theory, Petri nets and Boolean networks[195][196] with broad applications within CEF. Their collaborations cover diverse topics from plant metabolomics,[197] to human signal transduction networks[198] and the dissection of the macromolecular complexome.[199][200]

Organisation edit

The CEF Assembly coordinated the research and elected the CEF Speaker and the CEF Board of Directors. The CEF Assembly consisted of the Principal Investigators, Adjunct Investigators, Senior Investigators as well as Associated Members. Speakers of CEF included Werner Müller-Esterl (Nov 2006-Jan 2009), Harald Schwalbe (Feb 2009 - Feb 2013) and Volker Dötsch (March 2013 - October 2019).[201][202]

Publications edit

CEF scientists published more than 2600 original research publications (incl. 479 research papers in journals with an impact factor of ≥10) during the Cluster's lifetime. A full list can be found here.

Honours and prizes awarded to CEF scientists edit

A full list can be found here.

External links edit

References edit

  1. ^ "Method of the Year 2010". Nature Methods. 8 (1): 1. 2010. doi:10.1038/nmeth.f.321.
  2. ^ "Light-sheet fluorescence microscopy can image living samples in three dimensions with relatively low phototoxicity and at high speed". Nature Methods. 12 (1): 1. 2014. doi:10.1038/nmeth.3251. PMID 25699311.
  3. ^ Hunte C, Zickermann V, Brandt U (2010). "Functional modules and structural basis of conformational coupling in mitochondrial complex I". Science. 329 (5990): 448–51. Bibcode:2010Sci...329..448H. doi:10.1126/science.1191046. PMID 20595580. S2CID 11159551.
  4. ^ Zickermann V, Wirth C, Nasiri H, Siegmund K, Schwalbe H, Hunte C, Brandt U (2015). "Mechanistic insight from the crystal structure of mitochondrial complex I". Science. 347 (6217): 44–49. Bibcode:2015Sci...347...44Z. doi:10.1126/science.1259859. PMID 25554780. S2CID 23582849.
  5. ^ Hahn A, Parey K, Bublitz M, Mills Deryck J, Zickermann V, Vonck J, Kühlbrandt W, Meier T (2016). "Structure of a complete ATP synthase dimer reveals the molecular basis of inner mitochondrial membrane morphology". Mol Cell. 63 (3): 445–56. doi:10.1016/j.molcel.2016.05.037. PMC 4980432. PMID 27373333.
  6. ^ Mühleip AW, Joos F, Wigge C, Frangakis AS, Kühlbrandt W, Davies KM (2016). "Helical arrays of U-shaped ATP synthase dimers form tubular cristae in ciliate mitochondria". Proc Natl Acad Sci USA. 113 (30): 8442–8447. Bibcode:2016PNAS..113.8442M. doi:10.1073/pnas.1525430113. PMC 4968746. PMID 27402755.
  7. ^ Murphy BJ, Klusch N, Langer J, Mills DJ, Yildiz O, Kühlbrandt W (2019). "Rotary substates of mitochondrial ATP synthase reveal the basis of flexible F1-Fo coupling". Science. 364 (6446): eaaw9128. Bibcode:2019Sci...364.9128M. doi:10.1126/science.aaw9128. PMID 31221832. S2CID 195188479.
  8. ^ Hahn A, Vonck J, Mills DJ, Meier T, Kühlbrandt W (2018). "Structure, mechanism, and regulation of the chloroplast ATP synthase". Science. 360 (6389): 620. doi:10.1126/science.aat4318. PMC 7116070. PMID 29748256.
  9. ^ Davies KM, Strauss M, Daum B, Kief JH, Osiewacz HD, Rycovska A, Zickermann V, Kühlbrandt W (2011). "Macromolecular organization of ATP synthase and complex I in whole mitochondria". Proc Natl Acad Sci USA. 108 (34): 14121–14126. Bibcode:2011PNAS..10814121D. doi:10.1073/pnas.1103621108. PMC 3161574. PMID 21836051.
  10. ^ Davies KM, Blum TB, Kühlbrandt W (2018). "Conserved in situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants". Proc Natl Acad Sci USA. 115 (12): 3024–3029. Bibcode:2018PNAS..115.3024D. doi:10.1073/pnas.1720702115. PMC 5866595. PMID 29519876.
  11. ^ Buschmann S, Warkentin E, Xie H, Langer JD, Ermler U, Michel H (2010). "The structure of cbb3 cytochrome oxidase provides insights into proton pumping". Science. 329 (5989): 327–329. Bibcode:2010Sci...329..327B. doi:10.1126/science.1187303. PMID 20576851. S2CID 5083670.
  12. ^ Safarian S, Rajendran C, Müller H, Preu J, Langer JD, Ovchinnikov S, Hirose T, Kusumoto T, Sakamoto J, Michel H (2016). "Structure of a bd oxidase indicates similar mechanisms for membrane-integrated oxygen reductases". Science. 352 (6285): 583–586. Bibcode:2016Sci...352..583S. doi:10.1126/science.aaf2477. PMC 5515584. PMID 27126043.
  13. ^ Marcia M, Ermler U, Peng GH, Michel H (2009). "The structure of Aquifex aeolicus sulfide:quinone oxidoreductase, a basis to understand sulfide detoxification and respiration". Proc Natl Acad Sci USA. 106 (24): 9625–9630. Bibcode:2009PNAS..106.9625M. doi:10.1073/pnas.0904165106. PMC 2689314. PMID 19487671.
  14. ^ Bausewein T, Mills DJ, Langer JD, Nitschke B, Nussberger S, Kühlbrandt W (2017). "Cryo-EM structure of the TOM core complex from Neurospora crassa". Cell. 170 (4): 693–700.e7. doi:10.1016/j.cell.2017.07.012. PMID 28802041.
  15. ^ Diskowski M, Mehdipour AR, Wunnicke D, Mills DJ, Mikusevic V, Bärland N, Hoffmann J, Morgner N, Steinhoff HJ, Hummer G, Vonck J, Hänelt I (2017). "Helical jackknives control the gates of the double-pore K+ uptake system KtrAB". eLife. 6: e24303. doi:10.7554/eLife.24303. PMC 5449183. PMID 28504641.
  16. ^ Schulze S, Koster S, Geldmacher U, Terwisscha van Scheltinga AC, Kühlbrandt W (2010). "Structural basis of Na+-independent and cooperative substrate/product antiport in CaiT" (PDF). Nature. 467 (7312): 233–6. Bibcode:2010Natur.467..233S. doi:10.1038/nature09310. PMID 20829798. S2CID 4341977.
  17. ^ Ressl S, Terwisscha van Scheltinga AC, Vonrhein C, Ott V, Ziegler C (2009). "Molecular basis of transport and regulation in the Na+/betaine symporter BetP" (PDF). Nature. 458 (7234): 47–52. Bibcode:2009Natur.458...47R. doi:10.1038/nature07819. PMID 19262666. S2CID 205216142.
  18. ^ Eicher T, Seeger MA, Anselmi C, Zhou W, Brandstätter L, Verrey F, Diederichs K, Faraldo-Gómez JD, Pos KM (2014). "Coupling of remote alternating-access transport mechanisms for protons and substrates in the multidrug efflux pump AcrB". eLife. 3: e03145. doi:10.7554/eLife.03145.001. PMC 4359379. PMID 25248080.
  19. ^ Eicher T, Cha HJ, Seeger MA, Brandstatter L, El-Delik J, Bohnert JA, Kern WV, Verrey F, Grutter MG, Diederichs K, Pos KM (2012). "Transport of drugs by the multidrug transporter AcrB involves an access and a deep binding pocket that are separated by a switch-loop". Proc Natl Acad Sci USA. 109 (15): 5687–92. Bibcode:2012PNAS..109.5687E. doi:10.1073/pnas.1114944109. PMC 3326505. PMID 22451937.
  20. ^ Thomas C, Tampé R (2017). "Structure of the TAPBPR–MHC I complex defines the mechanism of peptide loading and editing". Science. 358 (6366): 1060–1064. Bibcode:2017Sci...358.1060T. doi:10.1126/science.aao6001. PMID 29025996.
  21. ^ Blees A, Januliene D, Hofmann T, Koller N, Schmidt C, Trowitzsch S, Moeller A, Tampé R (2017). "Structure of the human MHC-I peptide-loading complex". Nature. 551 (7681): 525–528. Bibcode:2017Natur.551..525B. doi:10.1038/nature24627. PMID 29107940. S2CID 4447406.
  22. ^ Lehnert E, Mao J, Mehdipour AR, Hummer G, Abele R, Glaubitz C, Tampé R (2016). "Antigenic peptide recognition on the human ABC transporter TAP resolved by DNP-enhanced solid-state NMR spectroscopy". J Am Chem Soc. 138 (42): 13967–13974. doi:10.1021/jacs.6b07426. PMID 27659210.
  23. ^ Barth K, Hank S, Spindler PE, Prisner TF, Tampé R, Joseph B (2018). "Conformational coupling and trans-inhibition in the human antigen transporter ortholog TmrAB resolved with dipolar EPR spectroscopy". J Am Chem Soc. 140 (13): 4527–4533. doi:10.1021/jacs.7b12409. PMID 29308886.
  24. ^ Kaur H, Lakatos-Karoly A, Vogel R, Nöll A, Tampé R, Glaubitz C (2016). "Coupled ATPase-adenylate kinase activity in ABC transporters". Nat Commun. 7: 13864. Bibcode:2016NatCo...713864K. doi:10.1038/ncomms13864. PMC 5192220. PMID 28004795.
  25. ^ Hellmich UA, Lyubenova S, Kaltenborn E, Doshi R, van Veen HW, Prisner TF, Glaubitz C (2012). "Probing the ATP hydrolysis cycle of the ABC multidrug transporter LmrA by pulsed EPR spectroscopy". J Am Chem Soc. 134 (13): 5857–62. doi:10.1021/ja211007t. PMID 22397466.
  26. ^ Ong YS, Lakatos A, Becker-Baldus J, Pos KM, Glaubitz C (2013). "Detecting substrates bound to the secondary multidrug efflux pump EmrE by DNP-enhanced solid-state NMR". J Am Chem Soc. 135 (42): 15754–62. doi:10.1021/Ja402605s. PMID 24047229.
  27. ^ Hempelmann F, Hölper S, Verhoefen MK, Woerner AC, Köhler T, Fiedler SA, Pfleger N, Wachtveitl J, Glaubitz C (2011). "The His75-Asp97 cluster in green proteorhodopsin". J Am Chem Soc. 133 (12): 4645–4654. doi:10.1021/ja111116a. PMID 21366243.
  28. ^ Reckel S, Gottstein D, Stehle J, Löhr F, Verhoefen MK, Takeda M, Silvers R, Kainosho M, Glaubitz C, Wachtveitl J, Bernhard F, Schwalbe H, Güntert P, Dötsch V (2011). "Solution NMR structure of proteorhodopsin". Angewandte Chemie International Edition. 50 (50): 11942–11946. doi:10.1002/anie.201105648. PMC 4234116. PMID 22034093.
  29. ^ Maciejko J, Kaur J, Becker-Baldus J, Glaubitz C (2019). "Photocycle-dependent conformational changes in the proteorhodopsin cross-protomer Asp-His-Trp triad revealed by DNP-enhanced MAS-NMR". Proc Natl Acad Sci USA. 116 (17): 8342–8349. Bibcode:2019PNAS..116.8342M. doi:10.1073/pnas.1817665116. PMC 6486740. PMID 30948633.
  30. ^ Morgner N, Kleinschroth T, Barth HD, Ludwig B, Brutschy B (2007). "A novel approach to analyze membrane proteins by laser mass spectrometry: From protein subunits to the integral complex". J Am Soc Mass Spectrom. 18 (8): 1429–1438. doi:10.1016/j.jasms.2007.04.013. PMID 17544294.
  31. ^ Joedicke L, Mao J, Kuenze G, Reinhart C, Kalavacherla T, Jonker HR, Richter C, Schwalbe H, Meiler J, Preu J, Michel H, Glaubitz C (2018). "The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors". Nat Chem Biol. 14 (3): 284–290. doi:10.1038/nchembio.2551. PMC 7992120. PMID 29334381.
  32. ^ Dikic I, Elazar Z (2018). "Mechanism and medical implications of mammalian autophagy". Nat Rev Mol Cell Biol. 19 (6): 349–364. doi:10.1038/s41580-018-0003-4. PMID 29618831. S2CID 4594197.
  33. ^ Genau HM, Huber J, Baschieri F, Akutsu M, Dötsch V, Farhan H, Rogov V, Behrends C (2015). "CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling". Mol Cell. 57 (6): 995–1010. doi:10.1016/j.molcel.2014.12.040. PMID 25684205.
  34. ^ Wild P, Farhan H, McEwan DG, Wagner S, Rogov VV, Brady NR, Richter B, Korac J, Waidmann O, Choudhary C, Dötsch V, Bumann D, Dikic I (2011). "Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth". Science. 333 (6039): 228–33. Bibcode:2011Sci...333..228W. doi:10.1126/science.1205405. PMC 3714538. PMID 21617041.
  35. ^ Fiskin E, Bionda T, Dikic I, Behrends C (2016). "Global analysis of host and bacterial ubiquitinome in response to Salmonella Typhimurium infection". Mol Cell. 62 (6): 967–981. doi:10.1016/j.molcel.2016.04.015. PMID 27211868.
  36. ^ Bhogaraju S, Kalayil S, Liu Y, Bonn F, Colby T, Matic I, Dikic I (2016). "Phosphoribosylation of ubiquitin promotes serine ubiquitination and impairs conventional ubiquitination". Cell. 167 (6): 1636–1649.e13. doi:10.1016/j.cell.2016.11.019. PMID 27912065.
  37. ^ Kalayil S, Bhogaraju S, Bonn F, Shin D, Liu Y, Gan N, Basquin J, Grumati P, Luo ZQ, Dikic I (2018). "nsights into catalysis and function of phosphoribosyl-linked serine ubiquitination". Nature. 557 (7707): 734–738. Bibcode:2018Natur.557..734K. doi:10.1038/s41586-018-0145-8. PMC 5980784. PMID 29795347.
  38. ^ Bhogaraju S, Bonn F, Mukherjee R, Adams M, Pfleiderer MM, Galej WP, Matkovic V, Lopez-Mosqueda J, Kalayil S, Shin D, Dikic I (2019). "Inhibition of bacterial ubiquitin ligases by SidJ-calmodulin-catalysed glutamylation". Nature. 572 (7769): 382–386. Bibcode:2019Natur.572..382B. doi:10.1038/s41586-019-1440-8. PMC 6715450. PMID 31330532.
  39. ^ Khaminets A, Heinrich T, Mari M, Grumati P, Huebner AK, Akutsu M, Liebmann L, Stolz A, Nietzsche S, Koch N, Mauthe M, Katona I, Qualmann B, Weis J, Reggiori F, Kurth I, Hübner CA, Dikic I (2015). "Regulation of endoplasmic reticulum turnover by selective autophagy". Nature. 522 (7556): 354–8. Bibcode:2015Natur.522..354K. doi:10.1038/nature14498. PMID 26040720. S2CID 4449106.
  40. ^ Bhaskara RM, Grumati P, Garcia-Pardo J, Kalayil S, Covarrubias-Pinto A, Chen W, Kudryashev M, Dikic I, Hummer G (2019). "Curvature induction and membrane remodeling by FAM134B reticulon homology domain assist selective ER-phagy". Nat Commun. 10 (1): 2370. Bibcode:2019NatCo..10.2370B. doi:10.1038/s41467-019-10345-3. PMC 6542808. PMID 31147549.
  41. ^ Husnjak K, Elsasser S, Zhang NX, Chen X, Randles L, Shi Y, Hofmann K, Walters KJ, Finley D, Dikic I (2008). "Proteasome subunit Rpn13 is a novel ubiquitin receptor". Nature. 453 (7194): 481–488. Bibcode:2008Natur.453..481H. doi:10.1038/nature06926. PMC 2839886. PMID 18497817.
  42. ^ Rahighi S, Ikeda F, Kawasaki M, Akutsu M, Suzuki N, Kato R, Kensche T, Uejima T, Bloor S, Komander D, Randow F, Wakatsuki S, Dikic I (2009). "Specific recognition of linear ubiquitin chains by NEMO is important for NF-κB activation". Cell. 136 (6): 1098–1109. doi:10.1016/j.cell.2009.03.007. PMID 19303852. S2CID 3683855.
  43. ^ Ikeda F, Deribe YL, Skånland SS, Stieglitz B, Grabbe C, Franz-Wachtel M, van Wijk SJ, Goswami P, Nagy V, Terzic J, Tokunaga F, Androulidaki A, Nakagawa T, Pasparakis M, Iwai K, Sundberg JP, Schaefer L, Rittinger K, Macek B, Dikic I (2011). "SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappa B activity and apoptosis". Nature. 471 (7340): 637–641. Bibcode:2011Natur.471..637I. doi:10.1038/nature09814. PMC 3085511. PMID 21455181.
  44. ^ von Delbrück M, Kniss A, Rogov VV, Pluska L, Bagola K, Löhr F, Güntert P, Sommer T, Dötsch V (2016). "The CUE domain of Cue1 aligns growing ubiquitin chains with Ubc7 for rapid elongation". Mol Cell. 62 (6): 918–928. doi:10.1016/j.molcel.2016.04.031. PMID 27264873.
  45. ^ van Wijk SJ, Fricke F, Herhaus L, Gupta J, Hötte K, Pampaloni F, Grumati P, Kaulich M, Sou YS, Komatsu M, Greten FR, Fulda S, Heilemann M, Dikic I (2017). "Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation". Nat Microbiol. 2 (7): 17066. doi:10.1038/nmicrobiol.2017.66. PMID 28481361. S2CID 1329736.
  46. ^ Kniss A, Schuetz D, Kazemi S, Pluska L, Spindler PE, Rogov VV, Husnjak K, Dikic I, Güntert P, Sommer T, Prisner TF, Dötsch V (2018). "Chain assembly and disassembly processes differently affect the conformational space of ubiquitin chains". Structure. 26 (2): 249–258.e4. doi:10.1016/j.str.2017.12.011. PMID 29358025.
  47. ^ Deutsch GB, Zielonka EM, Coutandin D, Weber TA, Schäfer B, Hannewald J, Luh LM, Durst FG, Ibrahim M, Hoffmann J, Niesen FH, Sentürk A, Kunkel H, Brutschy B, Schleiff E, Knapp S, Acker-Palmer A, Grez M, McKeon F, Dötsch V (2011). "DNA damage in oocytes induces a switch of the quality control factor TAp63a from dimer to tetramer". Cell. 144 (4): 566–576. doi:10.1016/j.cell.2011.01.013. PMC 3087504. PMID 21335238.
  48. ^ Coutandin D, Osterburg C, Srivastav RK, Sumyk M, Kehrloesser S, Gebel J, Tuppi M, Hannewald J, Schafer B, Salah E, Mathea S, Müller-Kuller U, Doutch J, Grez M, Knapp S, Dötsch V (2016). "Quality control in oocytes by p63 is based on a spring-loaded activation mechanism on the molecular and cellular level". eLife. 5: e13909. doi:10.7554/eLife.13909. PMC 4876613. PMID 27021569.
  49. ^ Tuppi M, Kehrloesser S, Coutandin DW, Rossi V, Luh LM, Strubel A, Hötte K, Hoffmeister M, Schäfer B, De Oliveira T, Greten F, Stelzer EH, Knapp S, De Felici M, Behrends C, Klinger FG, Dötsch V (2018). "Oocyte DNA damage quality control requires consecutive interplay of CHK2 and CK1 to activate p63". Nat Struct Mol Biol. 25 (3): 261–269. doi:10.1038/s41594-018-0035-7. PMID 29483652. S2CID 3685994.
  50. ^ Russo C, Osterburg C, Sirico A, Antonini D, Ambrosio R, Würz JM, Rinnenthal J, Ferniani M, Kehrloesser S, Schäfer B, Güntert P, Sinha S, Dötsch V, Missero (2018). "Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome". Proc Natl Acad Sci USA. 115 (5): E906–E915. Bibcode:2018PNAS..115E.906R. doi:10.1073/pnas.1713773115. PMC 5798343. PMID 29339502.
  51. ^ Benedikt A, Baltruschat S, Scholz B, Bursen A, Arrey TN, Meyer B, Varagnolo L, Müller AM, Karas M, Dingermann T, Marschalek R (2011). "The leukemogenic AF4-MLL fusion protein causes P-TEFb kinase activation and altered epigenetic signatures". Leukemia. 25 (1): 135–44. doi:10.1038/leu.2010.249. PMID 21030982.
  52. ^ Schmidt N, Kowald L, Wijk S, Fulda S (2019). "Differential involvement of TAK1, RIPK1 and NF-kappaB signaling in Smac mimetic-induced cell death in breast cancer cells". Biol Chem. 400 (2): 171–180. doi:10.1515/hsz-2018-0324. PMID 30391931. S2CID 53241442.
  53. ^ Belz K, Schoeneberger H, Wehner S, Weigert A, Bonig H, Klingebiel T, Fichtner I, Fulda S (2014). "Smac mimetic and glucocorticoids synergize to induce apoptosis in childhood ALL by promoting ripoptosome assembly". Blood. 124 (2): 240–50. doi:10.1182/blood-2013-05-500918. PMID 24855207.
  54. ^ Müller S; Ackloo S; Arrowsmith CH; Bauser M; Baryza JL; Blagg J; Böttcher J; Bountra C; Brown PJ; Bunnage ME; Carter AJ; Damerell D; Dötsch V; Drewry DH; Edwards AM; Edwards J; Elkins JM; Fischer C; Frye SV; Gollner A; Grimshaw CE; Ijzerman A; Hanke T; Hartung IV; Hitchcock S; Howe T; Hughes TV; Laufer S; Li VMJ; Liras S; Marsden BD; Matsui H; Mathias J; O'Hagan RC; Owen DR; Pande V; Rauh D; Rosenberg SH; Roth BL; Schneider NS; Scholten C; Singh Saikatendu K; Simeonov A; Takizawa M; Tse C; Thompson PR; Treiber DK; Viana AYI; Wells CI; Willson TM; Zuercher WJ; Knapp S; Mueller-Fahrnow A (2018). "Donated chemical probes for open science". eLife. 7: e34311. doi:10.7554/eLife.34311. PMC 5910019. PMID 29676732.
  55. ^ Wu Q, Heidenreich D, Zhou S, Ackloo S, Krämer A, Nakka K, Lima-Fernandes E, Deblois G, Duan S, Vellanki RN, Li F, Vedadi M, Dilworth J, Lupien M, Brennan PE, Arrowsmith CH, Müller S, Fedorov O, Filippakopoulos P, Knapp S (2019). "A chemical toolbox for the study of bromodomains and epigenetic signaling". Nat Commun. 10 (10: 1915): 1915. Bibcode:2019NatCo..10.1915W. doi:10.1038/s41467-019-09672-2. PMC 6478789. PMID 31015424.
  56. ^ Sawamiphak S, Seidel S, Essmann CL, Wilkinson GA, Pitulescu ME, Acker T, Acker-Palmer A (2010). "Ephrin-B2 regulates VEGFR2 function in developmental and tumour angiogenesis". Nature. 465 (7297): 487–91. Bibcode:2010Natur.465..487S. doi:10.1038/nature08995. PMID 20445540. S2CID 4423684.
  57. ^ Essmann CL, Martinez E, Geiger JC, Zimmer M, Traut MH, Stein V, Klein R, Acker-Palmer A (2008). "Serine phosphorylation of ephrinB2 regulates trafficking of synaptic AMPA receptors". Nat Neurosci. 11 (9): 1035–1043. doi:10.1038/nn.2171. PMID 19160501. S2CID 698572.
  58. ^ Stefer S, Reitz S, Wang F, Wild K, Pang YY, Schwarz D, Bomke J, Hein C, Löhr F, Bernhard F, Denic V, Dötsch V, Sinning I (2011). "Structural basis for tail-anchored membrane protein biogenesis by the Get3-receptor complex". Science. 333 (6043): 758–62. Bibcode:2011Sci...333..758S. doi:10.1126/science.1207125. PMC 3601824. PMID 21719644.
  59. ^ Cherepanov AV, Glaubitz C, Schwalbe H (2010). "High-resolution studies of uniformly 13C,15N-labeled RNA by solid-state NMR spectroscopy". Angewandte Chemie International Edition. 49 (28): 4747–50. doi:10.1002/anie.200906885. PMID 20533472.
  60. ^ Schnieders R, Wolter AC, Richter C, Wöhnert J, Schwalbe H, Fürtig B (2019). "Novel (13) C-detected NMR experiments for the precise detection of RNA structure". Angewandte Chemie International Edition. 58 (27): 9140–9144. doi:10.1002/anie.201904057. PMC 6617721. PMID 31131949.
  61. ^ Buck J, Fürtig B, Noeske J, Wöhnert J, Schwalbe H (2007). "Time-resolved NMR methods resolving ligand-induced RNA folding at atomic resolution". Proc Natl Acad Sci USA. 104 (40): 15699–704. Bibcode:2007PNAS..10415699B. doi:10.1073/pnas.0703182104. PMC 2000436. PMID 17895388.
  62. ^ Krstic I, Frolow O, Sezer D, Endeward B, Weigand JE, Suess B, Engels JW, Prisner TF (2010). "PELDOR spectroscopy reveals preorganization of the neomycin-responsive riboswitch tertiary structure". J Am Chem Soc. 132 (5): 1454–5. doi:10.1021/ja9077914. PMID 20078041.
  63. ^ Schiemann O, Piton N, Plackmeyer J, Bode BE, Prisner TF, Engels JW (2007). "Spin labeling of oligonucleotides with the nitroxide TPA and use of PELDOR, a pulse EPR method, to measure intramolecular distances". Nat Protoc. 2 (4): 904–23. doi:10.1038/nprot.2007.97. PMID 17446891. S2CID 6442268.
  64. ^ Weinrich T, Jaumann EA, Scheffer U, Prisner TF, Göbel MW (2018). "A cytidine phosphoramidite with protected nitroxide spin label: synthesis of a full-length TAR RNA and investigation by in-line probing and EPR spectroscopy". Chemistry: A European Journal. 24 (23): 6202–6207. doi:10.1002/chem.201800167. PMID 29485736.
  65. ^ Förster U, Grunewald C, Engels JW, Wachtveitl J (2010). "Ultrafast dynamics of 1-ethynylpyrene-modified RNA: a photophysical probe of intercalation". J Phys Chem B. 114 (35): 11638–45. doi:10.1021/jp103176q. PMID 20707369.
  66. ^ Gustmann H, Segler AJ, Gophane DB, Reuss AJ, Grünewald C, Braun M, Weigand JE, Sigurdsson ST, Wachtveitl J (2019). "Structure guided fluorescence labeling reveals a two-step binding mechanism of neomycin to its RNA aptamer". Nucleic Acids Res. 47 (1): 15–28. doi:10.1093/nar/gky1110. PMC 6326822. PMID 30462266.
  67. ^ Reining A, Nozinovic S, Schlepckow K, Buhr F, Fürtig B, Schwalbe H (2013). "Three-state mechanism couples ligand and temperature sensing in riboswitches". Nature. 499 (7458): 355–9. Bibcode:2013Natur.499..355R. doi:10.1038/Nature12378. PMID 23842498. S2CID 4414719.
  68. ^ Ferner J, Suhartono M, Breitung S, Jonker HR, Hennig M, Wöhnert J, Gobel M, Schwalbe H (2009). "Structures of HIV TAR RNA-ligand complexes reveal higher binding stoichiometries". ChemBioChem. 10 (9): 1490–1494. doi:10.1002/cbic.200900220. PMID 19444830. S2CID 44300779.
  69. ^ Morgner N, Barth HD, Brutschy B, Scheffer U, Breitung S, Gobel M (2008). "Binding sites of the viral RNA element TAR and of TAR mutants for various peptide ligands, probed with LILBID: A new laser mass spectrometry". J Am Soc Mass Spectrom. 19 (11): 1600–1611. doi:10.1016/j.jasms.2008.07.001. PMID 18693035.
  70. ^ Manoharan V, Fürtig B, Jaschke A, Schwalbe H (2009). "Metal-induced folding of diels-alderase ribozymes studied by static and time-resolved NMR spectroscopy". J Am Chem Soc. 131 (17): 6261–6270. doi:10.1021/ja900244x. PMID 19354210.
  71. ^ Kortmann J, Sczodrok S, Rinnenthal J, Schwalbe H, Narberhaus F (2011). "Translation on demand by a simple RNA-based thermosensor". Nucleic Acids Res. 39 (7): 2855–2868. doi:10.1093/nar/gkq1252. PMC 3074152. PMID 21131278.
  72. ^ Duchardt-Ferner E, Weigand JE, Ohlenschlager O, Schtnidtke SR, Suess B, Wöhnert J (2010). "Highly modular structure and ligand binding by conformational capture in a minimalistic riboswitch". Angewandte Chemie International Edition. 49 (35): 6216–6219. doi:10.1002/anie.201001339. PMID 20632338.
  73. ^ Steinert H, Sochor F, Wacker A, Buck J, Helmling C, Hiller F, Keyhani S, Noeske J, Grimm SK, Rudolph MM, Keller H, Mooney RA, Landick R, Suess B, Fürtig B, Wöhnert J, Schwalbe H (2017). "Pausing guides RNA folding to populate transiently stable RNA structures for riboswitch-based transcription regulation". eLife. 6: e21297. doi:10.7554/eLife.21297. PMC 5459577. PMID 28541183.
  74. ^ Neyer S, Kunz M, Geiss C, Hantsche M, Hodirnau VV, Seybert A, Engel C, Scheffer MP, Cramer P, Frangakis AS (2016). "Structure of RNA polymerase I transcribing ribosomal DNA genes". Nature. 540 (7634): 607–610. Bibcode:2016Natur.540..607N. doi:10.1038/nature20561. PMID 27842382. S2CID 205252425.
  75. ^ Meyer B, Wurm JP, Kotter P, Leisegang MS, Schilling V, Buchhaupt M, Held M, Bahr U, Karas M, Heckel A, Bohnsack MT, Wöhnert J, Entian KD (2011). "The Bowen-Conradi syndrome protein Nep1 (Emg1) has a dual role in eukaryotic ribosome biogenesis, as an essential assembly factor and in the methylation of Psi 1191 in yeast 18S rRNA". Nucleic Acids Res. 39 (4): 1526–37. doi:10.1093/nar/gkq931. PMC 3045603. PMID 20972225.
  76. ^ Wurm JP, Meyer B, Bahr U, Held M, Frolow O, Kotter P, Engels JW, Heckel A, Karas M, Entian KD, Wöhnert J (2010). "The ribosome assembly factor Nep1 responsible for Bowen-Conradi syndrome is a pseudouridine-N1-specific methyltransferase". Nucleic Acids Res. 38 (7): 2387–98. doi:10.1093/nar/gkp1189. PMC 2853112. PMID 20047967.
  77. ^ Bohnsack MT, Martin R, Granneman S, Ruprecht M, Schleiff E, Tollervey D (2009). "Prp43 bound at different sites on the pre-rRNA performs distinct functions in ribosome synthesis". Mol Cell. 36 (4): 583–92. doi:10.1016/j.molcel.2009.09.039. PMC 2806949. PMID 19941819.
  78. ^ Palm D, Streit D, Shanmugam T, Weis BL, Ruprecht M, Simm S, Schleiff E (2019). "Plant-specific ribosome biogenesis factors in Arabidopsis thaliana with essential function in rRNA processing". Nucleic Acids Res. 47 (4): 1880–1895. doi:10.1093/nar/gky1261. PMC 6393314. PMID 30576513.
  79. ^ Weis BL, Missbach S, Marzi J, Bohnsack MT, Schleiff E (2014). "The 60S associated ribosome biogenesis factor LSG1-2 is required for 40S maturation in Arabidopsis thaliana". Plant J. 80 (6): 1043–56. doi:10.1111/tpj.12703. PMID 25319368.
  80. ^ Endesfelder U, Finan K, Holden SJ, Cook PR, Kapanidis AN, Heilemann M (2013). "Multiscale spatial organization of RNA polymerase in Escherichia coli". Biophys J. 105 (1): 172–181. Bibcode:2013BpJ...105..172E. doi:10.1016/j.bpj.2013.05.048. PMC 3699759. PMID 23823236.
  81. ^ Stellos K, Gatsiou A, Stamatelopoulos K, Perisic Matic L, John D, Lunella FF, Jae N, Rossbach O, Amrhein C, Sigala F, Boon RA, Furtig B, Manavski Y, You X, Uchida S, Keller T, Boeckel JN, Franco-Cereceda A, Maegdefessel L, Chen W, Schwalbe H, Bindereif A, Eriksson P, Hedin U, Zeiher AM, Dimmeler S (2016). "Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation". Nat Med. 22 (10): 1140–1150. doi:10.1038/nm.4172. PMID 27595325. S2CID 3397638.
  82. ^ Müller-McNicoll M, Botti V, Domingues AM, Brandl H, Schwich OD, Steiner MC, Curk T, Poser I, Zarnack K, Neugebauer KM (2016). "SR proteins are NXF1 adaptors that link alternative RNA processing to mRNA export". Genes Dev. 30 (5): 553–66. doi:10.1101/gad.276477.115. PMC 4782049. PMID 26944680.
  83. ^ Braun S, Enculescu M, Setty ST, Cortes-Lopez M, de Almeida BP, Sutandy FX, Schulz L, Busch A, Seiler M, Ebersberger S, Barbosa-Morais NL, Legewie S, König J, Zarnack K (2018). "Decoding a cancer-relevant splicing decision in the RON proto-oncogene using high-throughput mutagenesis". Nat Commun. 9 (1): 3315. Bibcode:2018NatCo...9.3315B. doi:10.1038/s41467-018-05748-7. PMC 6098099. PMID 30120239.
  84. ^ Sambandan S, Akbalik G, Kochen L, Rinne J, Kahlstatt J, Glock C, Tushev G, Alvarez-Castelao B, Heckel A, Schuman EM (2017). "Activity-dependent spatially localized miRNA maturation in neuronal dendrites". Science. 355 (6325): 634–637. Bibcode:2017Sci...355..634S. doi:10.1126/science.aaf8995. PMID 28183980. S2CID 17159252.
  85. ^ Boon RA, Hofmann P, Michalik KM, Lozano-Vidal N, Berghauser D, Fischer A, Knau A, Jae N, Schurmann C, Dimmeler S (2016). "Long noncoding RNA Meg3 controls endothelial cell aging and function implications for regenerative angiogenesis". J Am Coll Cardiol. 68 (23): 2589–2591. doi:10.1016/j.jacc.2016.09.949. PMID 27931619.
  86. ^ Michalik KM, You X, Manavski Y, Doddaballapur A, Zörnig M, Braun T, John D, Ponomareva Y, Chen W, Uchida S, Boon RA, Dimmeler S (2014). "Long noncoding RNA MALAT1 regulates endothelial cell function and vessel growth". Circ Res. 114 (9): 1389–1397. doi:10.1161/circresaha.114.303265. PMID 24602777.
  87. ^ Cremer S, Michalik KM, Fischer A, Pfisterer L, Jaé N, Winter C, Boon RA, Muhly-Reinholz M, John D, Uchida S, Weber C, Poller W, Günther S, Braun T, Li DY, Maegdefessel L, Matic Perisic L, Hedin U, Soehnlein O, Zeiher A, Dimmeler S (2019). "Hematopoietic deficiency of the long non-coding RNA MALAT1 promotes atherosclerosis and plaque inflammation". Circulation. 139 (10): 1320–1334. doi:10.1161/circulationaha.117.029015. PMID 30586743. S2CID 58561771.
  88. ^ Nagel G, Szellas T, Huhn W, Kateriya S, Adeishvili N, Berthold P, Ollig D, Hegemann P, Bamberg E (2003). "Channelrhodopsin-2, a directly light-gated cation-selective membrane channel". Proc Natl Acad Sci USA. 100 (24): 13940–5. Bibcode:2003PNAS..10013940N. doi:10.1073/pnas.1936192100. PMC 283525. PMID 14615590.
  89. ^ Boyden ES, Zhang F, Bamberg E, Nagel G, Deisseroth K (2005). "Millisecond-timescale, genetically targeted optical control of neural activity". Nat Neurosci. 8 (9): 1263–1268. doi:10.1038/nn1525. PMID 16116447. S2CID 6809511.
  90. ^ Feldbauer K, Zimmermann D, Pintschovius V, Spitz J, Bamann C, Bamberg E (2009). "Channelrhodopsin-2 is a leaky proton pump". Proc Natl Acad Sci USA. 106 (30): 12317–12322. Bibcode:2009PNAS..10612317F. doi:10.1073/pnas.0905852106. PMC 2718366. PMID 19590013.
  91. ^ Lorenz-Fonfria VA, Resler T, Krause N, Nack M, Gossing M, Fischer von Mollard G, Bamann C, Bamberg E, Schlesinger R, Heberle J (2013). "Transient protonation changes in channelrhodopsin-2 and their relevance to channel gating". Proc Natl Acad Sci USA. 110 (14): E1273-81. Bibcode:2013PNAS..110E1273L. doi:10.1073/pnas.1219502110. PMC 3619329. PMID 23509282.
  92. ^ Neumann-Verhoefen MK, Neumann K, Bamann C, Radu I, Heberle J, Bamberg E, Wachtveitl J (2013). "Ultrafast infrared spectroscopy on channelrhodopsin-2 reveals efficient energy transfer from the retinal chromophore to the protein". J Am Chem Soc. 135 (18): 6968–6976. doi:10.1021/Ja400554y. PMID 23537405.
  93. ^ Kleinlogel S, Terpitz U, Legrum B, Gokbuget D, Boyden ES, Bamann C, Wood PG, Bamberg E (2011). "A gene-fusion strategy for stoichiometric and co-localized expression of light-gated membrane proteins". Nat Methods. 8 (12): 1083–1088. doi:10.1038/nmeth.1766. PMID 22056675. S2CID 11567708.
  94. ^ Zhang F, Wang LP, Brauner M, Liewald JF, Kay K, Watzke N, Wood PG, Bamberg E, Nagel G, Gottschalk A, Deisseroth K (2007). "Multimodal fast optical interrogation of neural circuitry". Nature. 446 (7136): 633–9. Bibcode:2007Natur.446..633Z. doi:10.1038/nature05744. PMID 17410168. S2CID 4415339.
  95. ^ Oranth A, Schultheis C, Tolstenkov O, Erbguth K, Nagpal J, Hain D, Brauner M, Wabnig S, Steuer Costa W, McWhirter RD, Zels S, Palumbos S, Miller Iii DM, Beets I, Gottschalk A (2018). "Food sensation modulates locomotion by dopamine and neuropeptide signaling in a distributed neuronal network". Neuron. 100 (6): 1414–1428. doi:10.1016/j.neuron.2018.10.024. PMID 30392795.
  96. ^ Stirman JN, Crane MM, Husson SJ, Wabnig S, Schultheis C, Gottschalk A, Lu H (2011). "Real-time multimodal optical control of neurons and muscles in freely behaving Caenorhabditis elegans". Nat Methods. 8 (2): 153–8. doi:10.1038/nmeth.1555. PMC 3189501. PMID 21240278.
  97. ^ Liewald JF, Brauner M, Stephens GJ, Bouhours M, Schultheis C, Zhen M, Gottschalk A (2008). "Optogenetic analysis of synaptic function". Nat Methods. 5 (10): 895–902. doi:10.1038/nmeth.1252. PMID 18794862. S2CID 17102550.
  98. ^ Kittelmann M, Liewald JF, Hegermann J, Schultheiss C, Brauner M, Steuer Costa W, Wabnig S, Eimer S, Gottschalk A (2013). "In vivo synaptic recovery following optogenetic hyperstimulation". Proc Natl Acad Sci USA. 110 (32): E3007-16. Bibcode:2013PNAS..110E3007K. doi:10.1073/pnas.1305679110. PMC 3740886. PMID 23878262.
  99. ^ Azimi Hashemi N, Bergs AC, Schüler C, Scheiwe AR, Steuer Costa W, Bach M, Liewald JF, Gottschalk A (2019). "Rhodopsin-based voltage imaging tools for use in muscles and neurons of Caenorhabditis elegans". Proc Natl Acad Sci USA. 116 (34): 17051–17060. Bibcode:2019PNAS..11617051A. doi:10.1073/pnas.1902443116. PMC 6708366. PMID 31371514.
  100. ^ AzimiHashemi N, Erbguth K, Vogt A, Riemensperger T, Rauch E, Woodmansee D, Nagpal J, Brauner M, Sheves M, Fiala A, Kattner L, Trauner D, Hegemann P, Gottschalk A, Liewald JF (2014). "Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools". Nat Commun. 5: 5810. Bibcode:2014NatCo...5.5810A. doi:10.1038/Ncomms6810. PMID 25503804.
  101. ^ Gao SQ, Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A (2015). "Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp". Nat Commun. 6: 8046. Bibcode:2015NatCo...6.8046G. doi:10.1038/ncomms9046. PMC 4569695. PMID 26345128.
  102. ^ Verhoefen MK, Bamann C, Blöcher R, Förster U, Bamberg E, Wachtveitl J (2010). "The photocycle of channelrhodopsin-2: ultrafast reaction dynamics and subsequent reaction steps". ChemPhysChem. 11 (14): 3113–22. doi:10.1002/cphc.201000181. PMID 20730849.
  103. ^ Volkov O, Kovalev K, Polovinkin V, Borshchevskiy V, Bamann C, Astashkin R, Marin E, Popov A, Balandin T, Willbold D, Buldt G, Bamberg E, Gordeliy V (2017). "Structural insights into ion conduction by channelrhodopsin 2". Science. 358 (6366): eaan8862. doi:10.1126/science.aan8862. PMID 29170206.
  104. ^ Kleinlogel S, Feldbauer K, Dempski RE, Fotis H, Wood PG, Bamann C, Bamberg E (2011). "Ultra light-sensitive and fast neuronal activation with the Ca(2+)-permeable channelrhodopsin CatCh" (PDF). Nat Neurosci. 14 (4): 513–8. doi:10.1038/nn.2776. PMID 21399632. S2CID 5907240.
  105. ^ Becker-Baldus J, Bamann C, Saxena K, Gustmann H, Brown LJ, Brown RC, Reiter C, Bamberg E, Wachtveitl J, Schwalbe H, Glaubitz C (2015). "Enlightening the photoactive site of channelrhodopsin-2 by DNP-enhanced solid-state NMR spectroscopy". Proc Natl Acad Sci USA. 112 (32): 9896–901. Bibcode:2015PNAS..112.9896B. doi:10.1073/pnas.1507713112. PMC 4538646. PMID 26216996.
  106. ^ Bamann C, Bamberg E, Wachtveitl J, Glaubitz C (2014). "Proteorhodopsin". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1837 (5): 614–25. doi:10.1016/j.bbabio.2013.09.010. PMID 24060527.
  107. ^ Mao JF, Do NN, Scholz F, Reggie L, Mehler M, Lakatos A, Ong YS, Ullrich SJ, Brown LJ, Brown RC, Becker-Baldus J, Wachtveitl J, Glaubitz C (2014). "Structural basis of the green-blue color switching in proteorhodopsin as determined by NMR spectroscopy". J Am Chem Soc. 136 (50): 17578–17590. doi:10.1021/ja5097946. PMID 25415762.
  108. ^ Maciejko J, Mehler M, Kaur J, Lieblein T, Morgner N, Ouari O, Tordo P, Becker-Baldus J, Glaubitz C (2015). "Visualizing specific cross-protomer interactions in the homo-oligomeric membrane protein proteorhodopsin by dynamic-nuclear-polarization-enhanced solid-state NMR". J Am Chem Soc. 137 (28): 9032–9043. doi:10.1021/jacs.5b03606. PMID 26102160.
  109. ^ Maciejko J, Kaur J, Becker-Baldus J, Glaubitz C (2019). "Photocycle-dependent conformational changes in the proteorhodopsin cross-protomer Asp-His-Trp triad revealed by DNP-enhanced MAS-NMR". Proc Natl Acad Sci USA. 116 (17): 8342–8349. Bibcode:2019PNAS..116.8342M. doi:10.1073/pnas.1817665116. PMC 6486740. PMID 30948633.
  110. ^ Hempelmann F, Hölper S, Verhoefen MK, Woerner AC, Köhler T, Fiedler SA, Pfleger N, Wachtveitl J, Glaubitz C (2011). "The His75-Asp97 cluster in green proteorhodopsin". J Am Chem Soc. 133 (12): 4645–4654. doi:10.1021/ja111116a. PMID 21366243.
  111. ^ Mehler M, Eckert CE, Leeder AJ, Kaur J, Fischer T, Kubatova N, Brown LJ, Brown RC, Becker-Baldus J, Wachtveitl J, Glaubitz C (2017). "Chromophore distortions in photointermediates of proteorhodopsin visualized by dynamic nuclear polarization-enhanced solid-state NMR" (PDF). J Am Chem Soc. 139 (45): 16143–16153. doi:10.1021/jacs.7b05061. PMID 29027800.
  112. ^ Azimi Hashemi N, Erbguth K, Vogt A, Riemensperger T, Rauch E, Woodmansee D, Nagpal J, Brauner M, Sheves M, Fiala A, Kattner L, Trauner D, Hegemann P, Gottschalk A, Liewald JF (2014). "Synthetic retinal analogues modify the spectral and kinetic characteristics of microbial rhodopsin optogenetic tools". Nat Commun. 5: 5810. Bibcode:2014NatCo...5.5810A. doi:10.1038/Ncomms6810. PMID 25503804.
  113. ^ Gao SQ, Nagpal J, Schneider MW, Kozjak-Pavlovic V, Nagel G, Gottschalk A (2015). "Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp". Nat Commun. 6: 8046. Bibcode:2015NatCo...6.8046G. doi:10.1038/ncomms9046. PMC 4569695. PMID 26345128.
  114. ^ Husson SJ, Steuer Costa W, Wabnig S, Stirman JN, Watson JD, Spencer WC, Akerboom J, Looger LL, Treinin M, Miller DM 3rd, Lu H, Gottschalk A (2012). "Optogenetic analysis of a nociceptor neuron and network reveals ion channels acting downstream of primary sensors". Curr Biol. 22 (9): 743–52. doi:10.1016/j.cub.2012.02.066. PMC 3350619. PMID 22483941.
  115. ^ Oranth A, Schultheis C, Tolstenkov O, Erbguth K, Nagpal J, Hain D, Brauner M, Wabnig S, Steuer Costa W, McWhirter RD, Zels S, Palumbos S, Miller Iii DM, Beets I, Gottschalk A (2018). "Food sensation modulates locomotion by dopamine and neuropeptide signaling in a distributed neuronal network". Neuron. 100 (6): 1414–1428.e10. doi:10.1016/j.neuron.2018.10.024. PMID 30392795.
  116. ^ Steuer Costa W, Van der Auwera P, Glock C, Liewald JF, Bach M, Schüler C, Wabnig S, Oranth A, Masurat F, Bringmann H, Schoofs L, Stelzer EH, Fischer SC, Gottschalk A (2019). "A GABAergic and peptidergic sleep neuron as a locomotion stop neuron with compartmentalized Ca2+ dynamics". Nat Commun. 10 (1): 4095. Bibcode:2019NatCo..10.4095S. doi:10.1038/s41467-019-12098-5. PMC 6736843. PMID 31506439.
  117. ^ Buff MC, Schäfer F, Wulffen B, Müller J, Pötzsch B, Heckel A, Mayer G (2010). "Dependence of aptamer activity on opposed terminal extensions: improvement of light-regulation efficiency". Nucleic Acids Res. 38 (6): 2111–8. doi:10.1093/nar/gkp1148. PMC 2847219. PMID 20007153.
  118. ^ Joshi KB, Vlachos A, Mikat V, Deller T, Heckel A (2012). "Light-activatable molecular beacons with a caged loop sequence". Chem Commun. 48 (22): 2746–8. doi:10.1039/c2cc16654b. PMID 22159276.
  119. ^ Lotz TS, Halbritter T, Kaiser C, Rudolph MM, Kraus L, Groher F, Steinwand S, Wachtveitl J, Heckel A, Suess B (2019). "A light-responsive RNA aptamer for an azobenzene derivative". Nucleic Acids Res. 47 (4): 2029–2040. doi:10.1093/nar/gky1225. PMC 6393235. PMID 30517682.
  120. ^ Rohrbach F, Schäfer F, Fichte MA, Pfeiffer F, Müller J, Pötzsch B, Heckel A, Mayer G (2013). "Aptamer-guided caging for selective masking of protein domains". Angewandte Chemie International Edition. 52 (45): 11912–11915. doi:10.1002/anie.201306686. PMID 24127310.
  121. ^ Seyfried P, Eiden L, Grebenovsky N, Mayer G, Heckel A (2017). "Photo-tethers for the (multi-)cyclic, conformational caging of long oligonucleotides". Angewandte Chemie International Edition. 56 (1): 359–363. doi:10.1002/anie.201610025. PMID 27897376.
  122. ^ Keyhani S, Goldau T, Blümler A, Heckel A, Schwalbe H (2018). "Chemo-enzymatic synthesis of position-specifically modified RNA for biophysical studies including light control and NMR spectroscopy". Angewandte Chemie International Edition. 57 (37): 12017–12021. doi:10.1002/anie.201807125. PMID 30007102. S2CID 51629476.
  123. ^ Helmling C, Klötzner DP, Sochor F, Mooney RA, Wacker A, Landick R, Fürtig B, Heckel A, Schwalbe H (2018). "Life times of metastable states guide regulatory signaling in transcriptional riboswitches". Nat Commun. 9 (1): 944. Bibcode:2018NatCo...9..944H. doi:10.1038/s41467-018-03375-w. PMC 5838219. PMID 29507289.
  124. ^ Steinert HS, Schäfer F, Jonker HR, Heckel A, Schwalbe H (2014). "Influence of the absolute configuration of NPE-caged cytosine on DNA single base pair stability". Angewandte Chemie International Edition. 53 (4): 1072–1075. doi:10.1002/anie.201307852. PMID 24339185.
  125. ^ Schäfer F, Joshi KB, Fichte MA, Mack T, Wachtveitl J, Heckel A (2011). "Wavelength-selective uncaging of dA and dC residues". Org Lett. 13 (6): 1450–3. doi:10.1021/ol200141v. PMID 21341754.
  126. ^ Fichte MA, Weyel XM, Junek S, Schäfer F, Herbivo C, Goeldner M, Specht A, Wachtveitl J, Heckel A (2016). "Three-dimensional control of DNA hybridization by orthogonal two-color two-photon uncaging". Angewandte Chemie International Edition. 55 (31): 8948–8952. doi:10.1002/anie.201603281. PMID 27294300.
  127. ^ Becker Y, Unger E, Fichte MA, Gacek DA, Dreuw A, Wachtveitl J, Walla PJ, Heckel A (2018). "A red-shifted two-photon-only caging group for three-dimensional photorelease". Chem Sci. 9 (10): 2797–2802. doi:10.1039/c7sc05182d. PMC 5914290. PMID 29732066.
  128. ^ Thevarpadam J, Bessi I, Binas O, Gonçalves DP, Slavov C, Jonker HR, Richter C, Wachtveitl J, Schwalbe H, Heckel A (2016). "Photoresponsive formation of an intermolecular minimal G-quadruplex motif". Angewandte Chemie International Edition. 55 (8): 2738–2742. doi:10.1002/anie.201510269. PMID 26805928.
  129. ^ Sambandan S, Akbalik G, Kochen L, Rinne J, Kahlstatt J, Glock C, Tushev G, Alvarez-Castelao B, Heckel A, Schuman EM (2017). "Activity-dependent spatially localized miRNA maturation in neuronal dendrites". Science. 355 (6325): 634–637. Bibcode:2017Sci...355..634S. doi:10.1126/science.aaf8995. PMID 28183980. S2CID 17159252.
  130. ^ Lucas T, Schäfer F, Müller P, Emig S, Heckel A, Dimmeler S (2017). "Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice". Nat Commun. 8: 15162. Bibcode:2017NatCo...815162L. doi:10.1038/ncomms15162. PMC 5418571. PMID 28462946.
  131. ^ Ackermann D, Schmidt TL, Hannam JS, Purohit CS, Heckel A, Famulok M (2010). "A double-stranded DNA rotaxane". Nat Nanotechnol. 5 (6): 436–42. Bibcode:2010NatNa...5..436A. doi:10.1038/nnano.2010.65. PMID 20400967.
  132. ^ Grebenovsky N, Goldau T, Bolte M, Heckel A (2018). "Light regulation of DNA minicircle dimerization by utilizing azobenzene C-nucleosides". Chemistry: A European Journal. 24 (14): 3425–3428. doi:10.1002/chem.201706003. PMID 29418024.
  133. ^ Schmidt TL, Koeppel MB, Thevarpadam J, Goncalves DP, Heckel A (2011). "A light trigger for DNA nanotechnology". Small. 7 (15): 2163–7. doi:10.1002/smll.201100182. PMID 21638782.
  134. ^ Reining A, Nozinovic S, Schlepckow K, Buhr F, Fürtig B, Schwalbe H (2013). "Three-state mechanism couples ligand and temperature sensing in riboswitches". Nature. 499 (7458): 355–9. Bibcode:2013Natur.499..355R. doi:10.1038/Nature12378. PMID 23842498. S2CID 4414719.
  135. ^ Diederichs T, Pugh G, Dorey A, Xing Y, Burns JR, Hung Nguyen Q, Tornow M, Tampé R, Howorka S (2019). "Synthetic protein-conductive membrane nanopores built with DNA". Nat Commun. 10 (1): 5018. Bibcode:2019NatCo..10.5018D. doi:10.1038/s41467-019-12639-y. PMC 6828756. PMID 31685824.
  136. ^ Grunwald C, Schulze K, Reichel A, Weiss VU, Blaas D, Piehler J, Wiesmüller KH, Tampé R (2010). "In situ assembly of macromolecular complexes triggered by light". Proc Natl Acad Sci USA. 107 (14): 6146–6151. Bibcode:2010PNAS..107.6146G. doi:10.1073/pnas.0912617107. PMC 2852015. PMID 20200313.
  137. ^ Klein A, Hank S, Raulf A, Joest EF, Tissen F, Heilemann M, Wieneke R, Tampé R (2018). "Live-cell labeling of endogenous proteins with nanometer precision by transduced nanobodies". Chem Sci. 9 (40): 7835–7842. doi:10.1039/C8SC02910E. PMC 6194584. PMID 30429993.
  138. ^ Kollmannsperger A, Sharei A, Raulf A, Heilemann M, Langer R, Jensen KF, Wieneke R, Tampé R (2016). "Live-cell protein labelling with nanometre precision by cell squeezing". Nat Commun. 7: 10372. Bibcode:2016NatCo...710372K. doi:10.1038/ncomms10372. PMC 4740111. PMID 26822409.
  139. ^ Wieneke R, Raulf A, Kollmannsperger A, Heilemann M, Tampé R (2015). "Small labeling pair for single-molecule super-resolution imaging". Angewandte Chemie International Edition. 54 (35): 10216–9. doi:10.1002/anie.201503215. PMID 26201868.
  140. ^ Gatterdam V, Ramadass R, Stoess T, Fichte MA, Wachtveitl J, Heckel A, Tampé R (2014). "Three-dimensional protein networks assembled by two-photon activation". Angewandte Chemie International Edition. 53 (22): 5680–5684. doi:10.1002/anie.201309930. PMID 24729568.
  141. ^ Braner M, Koller N, Knauer J, Herbring V, Hank S, Wieneke R, Tampé R (2019). "Optical control of the antigen translocation by synthetic photo-conditional viral inhibitors". Chem Sci. 10 (7): 2001–2005. doi:10.1039/c8sc04863k. PMC 6385481. PMID 30881629.
  142. ^ Gajewski J, Buelens F, Serdjukow S, Janszen M, Cortina N, Grubmüller H, Grininger M (2017). "Engineering fatty acid synthases for directed polyketide production". Nat Chem Biol. 13 (4): 363–365. doi:10.1038/nchembio.2314. hdl:11858/00-001M-0000-002C-8359-6. PMID 28218912.
  143. ^ Gajewski J, Pavlovic R, Fischer M, Boles E, Grininger M (2017). "Engineering fungal de novo fatty acid synthesis for short chain fatty acid production". Nat Commun. 8: 14650. Bibcode:2017NatCo...814650G. doi:10.1038/ncomms14650. PMC 5353594. PMID 28281527.
  144. ^ Staudt H, Hoesl MG, Dreuw A, Serdjukow S, Oesterhelt D, Budisa N, Wachtveitl J, Grininger M (2013). "Directed manipulation of a flavoprotein photocycle". Angewandte Chemie International Edition. 52 (32): 8463–6. doi:10.1002/anie.201302334. PMID 23818044.
  145. ^ "Method of the Year 2015". Nature Methods. 13 (1): 1. January 2016. doi:10.1038/nmeth.3730. PMID 27110621.
  146. ^ "The Nobel Prize in Chemistry 2017". Retrieved 9 March 2020.
  147. ^ Allegretti M, Klusch N, Mills DJ, Vonck J, Kühlbrandt W, Davies KM (2015). "Horizontal membrane-intrinsic alpha-helices in the stator a-subunit of an F-type ATP synthase". Nature. 521 (7551): 237–40. Bibcode:2015Natur.521..237A. doi:10.1038/nature14185. PMID 25707805. S2CID 205242498.
  148. ^ Eltsov M, Dube N, Yu Z, Pasakarnis L, Haselmann-Weiss U, Brunner D, Frangakis AS (2015). "Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography". Nat Cell Biol. 17 (5): 605–14. doi:10.1038/ncb3159. PMID 25893916. S2CID 6543151.
  149. ^ Neyer S, Kunz M, Geiss C, Hantsche M, Hodirnau VV, Seybert A, Engel C, Scheffer MP, Cramer P, Frangakis AS (2016). "Structure of RNA polymerase I transcribing ribosomal DNA genes". Nature. 540 (7634): 607–610. Bibcode:2016Natur.540..607N. doi:10.1038/nature20561. PMID 27842382. S2CID 205252425.
  150. ^ Hahn A, Vonck J, Mills DJ, Meier T, Kühlbrandt W (2018). "Structure, mechanism, and regulation of the chloroplast ATP synthase". Science. 360 (6389): 620. doi:10.1126/science.aat4318. PMC 7116070. PMID 29748256.
  151. ^ Hofmann S, Januliene D, Mehdipour AR, Thomas C, Stefan E, Brüchert S, Kuhn BT, Geertsma ER, Hummer G, Tampé R, Moeller A (2019). "Conformation space of a heterodimeric ABC exporter under turnover conditions". Nature. 571 (7766): 580–583. doi:10.1038/s41586-019-1391-0. PMC 7612745. PMID 31316210. S2CID 197543295.
  152. ^ Faruqi AR, Henderson R (2007). "Electronic detectors for electron microscopy". Curr. Opin. Struct. Biol. 17 (5): 549–55. doi:10.1016/j.sbi.2007.08.014. PMID 17913494.
  153. ^ Kühlbrandt W (2014). "The resolution revolution". Science. 343 (6178): 1443–1444. Bibcode:2014Sci...343.1443K. doi:10.1126/science.1251652. PMID 24675944. S2CID 35524447.
  154. ^ Eltsov M, Dube N, Yu Z, Pasakarnis L, Haselmann-Weiss U, Brunner D, Frangakis AS (2015). "Quantitative analysis of cytoskeletal reorganization during epithelial tissue sealing by large-volume electron tomography". Nat Cell Biol. 17 (5): 605–14. doi:10.1038/ncb3159. PMID 25893916. S2CID 6543151.
  155. ^ Keller PJ, Schmidt AD, Santella A, Khairy K, Bao Z, Wittbrodt J, Stelzer EH (2010). "Fast, high-contrast imaging of animal development with scanned light sheet-based structured-illumination microscopy". Nat Methods. 7 (8): 637–642. doi:10.1038/nmeth.1476. PMC 4418465. PMID 20601950.
  156. ^ Stelzer EH (2015). "Light-sheet fluorescence microscopy for quantitative biology". Nat Methods. 12 (1): 23–26. doi:10.1038/nmeth.3219. PMID 25549266. S2CID 34063754.
  157. ^ "Method of the Year 2014". Nature Methods. 12 (1): 1. 2015. doi:10.1038/nmeth.3251. PMID 25699311.
  158. ^ Strobl F, Schmitz A, Stelzer EH (2015). "Live imaging of Tribolium castaneum embryonic development using light-sheet-based fluorescence microscopy". Nat Protoc. 10 (10): 1486–1507. doi:10.1038/nprot.2015.093. PMID 26334868. S2CID 24774566.
  159. ^ Strobl F, Schmitz A, Stelzer EH (2017). "Improving your four-dimensional image: traveling through a decade of light-sheet-based fluorescence microscopy research". Nat Protoc. 12 (6): 1103–1109. doi:10.1038/nprot.2017.028. PMID 28471459. S2CID 38354456.
  160. ^ von Wangenheim D, Fangerau J, Schmitz A, Smith RS, Leitte H, Stelzer EH, Maizel A (2016). "Rules and self-organizing properties of post-embryonic plant organ cell division patterns". Curr Biol. 26 (4): 439–449. doi:10.1016/j.cub.2015.12.047. hdl:11858/00-001M-0000-002B-1640-B. PMID 26832441.
  161. ^ Mathew B, Schmitz A, Munoz-Descalzo S, Ansari N, Pampaloni F, Stelzer EH, Fischer SC (2015). "Robust and automated three-dimensional segmentation of densely packed cell nuclei in different biological specimens with Lines-of-Sight decomposition". BMC Bioinformatics. 16: 187. doi:10.1186/s12859-015-0617-x. PMC 4458345. PMID 26049713.
  162. ^ Schmitz A, Fischer SC, Mattheyer C, Pampaloni F, Stelzer EH (2017). "Multiscale image analysis reveals structural heterogeneity of the cell microenvironment in homotypic spheroids". Sci Rep. 7: 43693. Bibcode:2017NatSR...743693S. doi:10.1038/srep43693. PMC 5334646. PMID 28255161.
  163. ^ Venkataramani V, Herrmannsdorfer F, Heilemann M, Kuner T (2016). "SuReSim: simulating localization microscopy experiments from ground truth models". Nat Methods. 13 (4): 319–321. doi:10.1038/Nmeth.3775. PMID 26928761. S2CID 3776898.
  164. ^ van Wijk SJ, Fricke F, Herhaus L, Gupta J, Hötte K, Pampaloni F, Grumati P, Kaulich M, Sou YS, Komatsu M, Greten FR, Fulda S, Heilemann M, Dikic I (2017). "Linear ubiquitination of cytosolic Salmonella Typhimurium activates NF-κB and restricts bacterial proliferation". Nat Microbiol. 2 (7): 17066. doi:10.1038/nmicrobiol.2017.66. PMID 28481361. S2CID 1329736.
  165. ^ Grumati P, Morozzi G, Holper S, Mari M, Harwardt MI, Yan R, Müller S, Reggiori F, Heilemann M, Dikic I (2017). "Full length RTN3 regulates turnover of tubular endoplasmic reticulum via selective autophagy". eLife. 6: e25555. doi:10.7554/eLife.25555. PMC 5517149. PMID 28617241.
  166. ^ Wieneke R, Raulf A, Kollmannsperger A, Heilemann M, Tampé R (2015). "Small labeling pair for single-molecule super-resolution imaging". Angewandte Chemie International Edition. 54 (35): 10216–9. doi:10.1002/anie.201503215. PMID 26201868.
  167. ^ Kollmannsperger A, Sharei A, Raulf A, Heilemann M, Langer R, Jensen KF, Wieneke R, Tampé R (2016). "Live-cell protein labelling with nanometre precision by cell squeezing". Nat Commun. 7: 10372. Bibcode:2016NatCo...710372K. doi:10.1038/ncomms10372. PMC 4740111. PMID 26822409.
  168. ^ Prandolini MJ, Denysenkov VP, Gafurov M, Endeward B, Prisner TF (2009). "High-field dynamic nuclear polarization in aqueous solutions". J Am Chem Soc. 131 (17): 6090–2. doi:10.1021/ja901496g. PMID 19361195.
  169. ^ Joedicke L, Mao J, Kuenze G, Reinhart C, Kalavacherla T, Jonker HR, Richter C, Schwalbe H, Meiler J, Preu J, Michel H, Glaubitz C (2018). "The molecular basis of subtype selectivity of human kinin G-protein-coupled receptors". Nat Chem Biol. 14 (3): 284–290. doi:10.1038/nchembio.2551. PMC 7992120. PMID 29334381.
  170. ^ Lehnert E, Mao J, Mehdipour AR, Hummer G, Abele R, Glaubitz C, Tampé R (2016). "Antigenic peptide recognition on the human ABC transporter TAP resolved by DNP-enhanced solid-state NMR spectroscopy". J Am Chem Soc. 138 (42): 13967–13974. doi:10.1021/jacs.6b07426. PMID 27659210.
  171. ^ Mehler M, Eckert CE, Leeder AJ, Kaur J, Fischer T, Kubatova N, Brown LJ, Brown RC, Becker-Baldus J, Wachtveitl J, Glaubitz C (2017). "Chromophore distortions in photointermediates of proteorhodopsin visualized by dynamic nuclear polarization-enhanced solid-state NMR" (PDF). J Am Chem Soc. 139 (45): 16143–16153. doi:10.1021/jacs.7b05061. PMID 29027800.
  172. ^ Krstić I, Hänsel R, Romainczyk O, Engels JW, Dötsch V, Prisner TF (2011). "Long-range distance measurements on nucleic acids in cells by pulsed EPR spectroscopy". Angewandte Chemie International Edition. 50 (22): 5070–5074. doi:10.1002/anie.201100886. PMID 21506223.
  173. ^ Barth K, Hank S, Spindler PE, Prisner TF, Tampé R, Joseph B (2018). "Conformational coupling and trans-inhibition in the human antigen transporter ortholog TmrAB resolved with dipolar EPR spectroscopy". J Am Chem Soc. 140 (13): 4527–4533. doi:10.1021/jacs.7b12409. PMID 29308886.
  174. ^ Morgner N, Hoffmann J, Barth HD, Meier T, Brutschy B (2008). "LILBID-mass spectrometry applied to the mass analysis of RNA polymerase II and an F1Fo-ATP synthase". Int J Mass Spectrom. 277 (1–3): 309–313. Bibcode:2008IJMSp.277..309M. doi:10.1016/j.ijms.2008.08.001.
  175. ^ Hellwig N, Peetz O, Ahdash Z, Tascon I, Booth PJ, Mikusevic V, Diskowski M, Politis A, Hellmich Y, Hanelt I, Reading E, Morgner N (2018). "ative mass spectrometry goes more native: investigation of membrane protein complexes directly from SMALPs". Chem Commun. 54 (97): 13702–13705. doi:10.1039/c8cc06284f. PMC 6289172. PMID 30452022.
  176. ^ Peetz O, Hellwig N, Henrich E, Mezhyrova J, Dötsch V, Bernhard F, Morgner N (2019). "LILBID and nESI: Different native mass spectrometry techniques as tools in structural biology". J Am Soc Mass Spectrom. 30 (1): 181–191. Bibcode:2019JASMS..30..181P. doi:10.1007/s13361-018-2061-4. PMC 6318263. PMID 30225732.
  177. ^ Angerer H, Schonborn S, Gorka J, Bahr U, Karas M, Wittig I, Heidler J, Hoffmann J, Morgner N, Zickermann V (2017). "Acyl modification and binding of mitochondrial ACP to multiprotein complexes". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1864 (10): 1913–1920. doi:10.1016/j.bbamcr.2017.08.006. PMID 28802701.
  178. ^ Diskowski M, Mehdipour AR, Wunnicke D, Mills DJ, Mikusevic V, Bärland N, Hoffmann J, Morgner N, Steinhoff HJ, Hummer G, Vonck J, Hänelt I (2017). "Helical jackknives control the gates of the double-pore K+ uptake system KtrAB". eLife. 6: e24303. doi:10.7554/eLife.24303. PMC 5449183. PMID 28504641.
  179. ^ Hoffmann J, Sokolova L, Preiss L, Hicks DB, Krulwich TA, Morgner N, Wittig I, Schägger H, Meier T, Brutschy B (2010). "ATP synthases: cellular nanomotors characterized by LILBID mass spectrometry". Phys Chem Chem Phys. 12 (41): 13375–13382. Bibcode:2010PCCP...1213375H. doi:10.1039/c0cp00733a. PMC 2955850. PMID 20820587.
  180. ^ Maciejko J, Mehler M, Kaur J, Lieblein T, Morgner N, Ouari O, Tordo P, Becker-Baldus J, Glaubitz C (2015). "Visualizing specific cross-protomer interactions in the homo-oligomeric membrane protein proteorhodopsin by dynamic-nuclear-polarization-enhanced solid-state NMR". J Am Chem Soc. 137 (28): 9032–9043. doi:10.1021/jacs.5b03606. PMID 26102160.
  181. ^ Kohl-Landgraf J, Braun M, Ozcoban C, Goncalves DP, Heckel A, Wachtveitl J (2012). "Ultrafast dynamics of a spiropyran in water". J Am Chem Soc. 134 (34): 14070–14077. doi:10.1021/ja304395k. PMID 22803805.
  182. ^ Steinwand S, Yu Z, Hecht S, Wachtveitl J (2016). "Ultrafast dynamics of photoisomerization and subsequent unfolding of an oligoazobenzene foldamer". J Am Chem Soc. 138 (39): 12997–13005. doi:10.1021/jacs.6b07720. PMID 27598007.
  183. ^ Förster U, Weigand JE, Trojanowski P, Suess B, Wachtveitl J (2012). "Conformational dynamics of the tetracycline-binding aptamer". Nucleic Acids Res. 40 (4): 1807–17. doi:10.1093/nar/gkr835. PMC 3287181. PMID 22053085.
  184. ^ Halbritter T, Kaiser C, Wachtveitl J, Heckel A (2017). "Pyridine-spiropyran derivative as a persistent, reversible photoacid in water". J Org Chem. 82 (15): 8040–8047. doi:10.1021/acs.joc.7b01268. PMID 28686024.
  185. ^ Gustmann H, Segler AJ, Gophane DB, Reuss AJ, Grünewald C, Braun M, Weigand JE, Sigurdsson ST, Wachtveitl J (2019). "Structure guided fluorescence labeling reveals a two-step binding mechanism of neomycin to its RNA aptamer". Nucleic Acids Res. 47 (1): 15–28. doi:10.1093/nar/gky1110. PMC 6326822. PMID 30462266.
  186. ^ Hofmann S, Januliene D, Mehdipour AR, Thomas C, Stefan E, Brüchert S, Kuhn BT, Geertsma ER, Hummer G, Tampé R, Moeller A (2019). "Conformation space of a heterodimeric ABC exporter under turnover conditions". Nature. 571 (7766): 580–583. doi:10.1038/s41586-019-1391-0. PMC 7612745. PMID 31316210. S2CID 197543295.
  187. ^ Shin D, Mukherjee R, Liu Y, Gonzalez A, Bonn F, Liu Y, Rogov VV, Heinz M, Stolz A, Hummer G, Dötsch V, Luo ZQ, Bhogaraju S, Dikic I (2020). "Regulation of phosphoribosyl-linked serine ubiquitination by deubiquitinases DupA and DupB". Mol Cell. 77 (1): 164–179.e6. doi:10.1016/j.molcel.2019.10.019. PMC 6941232. PMID 31732457.
  188. ^ Okazaki KI, Wöhlert D, Warnau J, Jung H, Yildiz O, Kühlbrandt W, Hummer G (2019). "Mechanism of the electroneutral sodium/proton antiporter PaNhaP from transition-path shooting". Nat Commun. 10 (1): 1742. Bibcode:2019NatCo..10.1742O. doi:10.1038/s41467-019-09739-0. PMC 6465308. PMID 30988359.
  189. ^ Halbleib K, Pesek K, Covino R, Hofbauer HF, Wunnicke D, Hänelt I, Hummer G, Ernst R (2017). "Activation of the unfolded protein response by lipid bilayer stress". Mol Cell. 67 (4): 673–684.e8. doi:10.1016/j.molcel.2017.06.012. PMID 28689662.
  190. ^ Lehnert E, Mao J, Mehdipour AR, Hummer G, Abele R, Glaubitz C, Tampé R (2016). "Antigenic peptide recognition on the human ABC transporter TAP resolved by DNP-enhanced solid-state NMR spectroscopy". J Am Chem Soc. 138 (42): 13967–13974. doi:10.1021/jacs.6b07426. PMID 27659210.
  191. ^ Koch I; Schäfer T (2018). "Protein super-secondary structure and quaternary structure topology: theoretical description and application". Current Opinion in Structural Biology. 50: 134–143. doi:10.1016/j.sbi.2018.02.005. PMID 29558676. S2CID 3991944.
  192. ^ Busch A, Brüggemann M, Ebersberger S, Zarnack K (2019). "iCLIP data analysis: A complete pipeline from sequencing reads to RBP binding sites". Methods. 178: 49–62. doi:10.1016/j.ymeth.2019.11.008. PMID 31751605.
  193. ^ Di Liddo A, de Oliveira Freitas Machado C, Fischer S, Ebersberger S, Heumuller AW, Weigand JE, Muller-McNicoll M, Zarnack K (2019). "A combined computational pipeline to detect circular RNAs in human cancer cells under hypoxic stress". J Mol Cell Biol. 11 (10): 829–844. doi:10.1093/jmcb/mjz094. PMC 6884703. PMID 31560396.
  194. ^ Haberman N, Huppertz I, Attig J, König J, Wang Z, Hauer C, Hentze MW, Kulozik AE, Le Hir H, Curk T, Sibley CR, Zarnack K, Ule J (2017). "Insights into the design and interpretation of iCLIP experiments". Genome Biol. 18 (1): 7. doi:10.1186/s13059-016-1130-x. PMC 5240381. PMID 28093074.
  195. ^ Einloft J; Ackermann J; Nothen J; Koch I (2013). "MonaLisa - visualization and analysis of functional modules in biochemical networks". Bioinformatics. 29 (11): 1469–70. doi:10.1093/bioinformatics/btt165. PMID 23564846.
  196. ^ Philipp O, Hamann A, Osiewacz HD, Koch I (2017). "The autophagy interaction network of the aging model Podospora anserina". BMC Bioinformatics. 18 (1): 196. doi:10.1186/s12859-017-1603-2. PMC 5369006. PMID 28347269.
  197. ^ Koch I, Nöthen J, Schleiff E (2017). "Modeling the metabolism of Arabidopsis thaliana: application of network decomposition and network reduction in the context of Petri nets". Front Genet. 8: 85. doi:10.3389/fgene.2017.00085. PMC 5491931. PMID 28713420.
  198. ^ Amstein L, Ackermann J, Scheidel J, Fulda S, Dikic I, Koch I (2017). "Manatee invariants reveal functional pathways in signaling networks". BMC Syst Biol. 11 (1): 72. doi:10.1186/s12918-017-0448-7. PMC 5534052. PMID 28754124.
  199. ^ Giese H, Ackermann J, Heide H, Bleier L, Drose S, Wittig I, Brandt U, Koch I (2015). "NOVA: a software to analyze complexome profiling data". Bioinformatics. 31 (3): 440–1. doi:10.1093/bioinformatics/btu623. PMID 25301849.
  200. ^ Heide H, Bleier L, Steger M, Ackermann J, Dröse S, Schwamb B, Zörnig M, Reichert AS, Koch I, Wittig I, Brandt U (2012). "Complexome profiling identifies TMEM126B as a component of the mitochondrial complex I assembly complex". Cell Metab. 16 (4): 538–549. doi:10.1016/j.cmet.2012.08.009. PMID 22982022.
  201. ^ "EXC 115: Macromolecular Complexes". GEPRIS Database of the Deutsche Forschungsgemeinschaft DFG. Retrieved 13 March 2020.
  202. ^ "Cluster of Excellence Macromolecular Complexs in Action" (PDF). CEF. Retrieved 13 March 2020.


Retrieved from "https://en.wikipedia.org/w/index.php?title=Cluster_of_Excellence_Frankfurt_Macromolecular_Complexes&oldid=1193272124"