Ferredoxins (from Latin ferrum: iron + redox, often abbreviated "fd") are iron–sulfur proteins that mediate electron transfer in a range of metabolic reactions. The term "ferredoxin" was coined by D.C. Wharton of the DuPont Co. and applied to the "iron protein" first purified in 1962 by Mortenson, Valentine, and Carnahan from the anaerobic bacterium Clostridium pasteurianum.
Another redox protein, isolated from spinach chloroplasts, was termed "chloroplast ferredoxin". The chloroplast ferredoxin is involved in both cyclic and non-cyclic photophosphorylation reactions of photosynthesis. In non-cyclic photophosphorylation, ferredoxin is the last electron acceptor thus reducing the enzyme NADP+ reductase. It accepts electrons produced from sunlight-excited chlorophyll and transfers them to the enzyme ferredoxin: NADP+ oxidoreductase EC 126.96.36.199.
Ferredoxins are small proteins containing iron and sulfur atoms organized as iron–sulfur clusters. These biological "capacitors" can accept or discharge electrons, with the effect of a change in the oxidation state of the iron atoms between +2 and +3. In this way, ferredoxin acts as an electron transfer agent in biological redox reactions.
Ferredoxins can be classified according to the nature of their iron–sulfur clusters and by sequence similarity.
|2Fe-2S iron-sulfur cluster binding domain|
Structural representation of an Fe2S2 ferredoxin.
|SCOPe||3fxc / SUPFAM|
Members of the 2Fe–2S ferredoxin superfamily (InterPro: IPR036010) have a general core structure consisting of beta(2)-alpha-beta(2), which includes putidaredoxin, terpredoxin, and adrenodoxin. They are proteins of around one hundred amino acids with four conserved cysteine residues to which the 2Fe–2S cluster is ligated. This conserved region is also found as a domain in various metabolic enzymes and in multidomain proteins, such as aldehyde oxidoreductase (N-terminal), xanthine oxidase (N-terminal), phthalate dioxygenase reductase (C-terminal), succinate dehydrogenase iron–sulphur protein (N-terminal), and methane monooxygenase reductase (N-terminal).
One group of ferredoxins, originally found in chloroplast membranes, has been termed "chloroplast-type" or "plant-type" (InterPro: IPR010241). Its active center is a [Fe2S2] cluster, where the iron atoms are tetrahedrally coordinated both by inorganic sulfur atoms and by sulfurs of four conserved cysteine (Cys) residues.
In chloroplasts, Fe2S2 ferredoxins function as electron carriers in the photosynthetic electron transport chain and as electron donors to various cellular proteins, such as glutamate synthase, nitrite reductase, sulfite reductase, and the cyclase of chlorophyll biosynthesis. Since the cyclase is a ferredoxin dependent enzyme this may provide a mechanism for coordination between photosynthesis and the chloroplasts need for chlorophyll by linking chlorophyll biosynthesis to the photosynthetic electron transport chain. In hydroxylating bacterial dioxygenase systems, they serve as intermediate electron-transfer carriers between reductase flavoproteins and oxygenase.
The Fe2S2 ferredoxin from Clostridium pasteurianum (Cp2FeFd; nitrogenase has been revealed. Homologous ferredoxins from Azotobacter vinelandii (Av2FeFdI; ) and Aquifex aeolicus (AaFd; ) have been characterized. The crystal structure of AaFd has been solved. AaFd exists as a dimer. The structure of AaFd monomer is different from other Fe2S2 ferredoxins. The fold belongs to the α+β class, with first four β-strands and two α-helices adopting a variant of the thioredoxin fold. UniProt categorizes these as the "2Fe2S Shethna-type ferredoxin" family.) has been recognized as distinct protein family on the basis of its amino acid sequence, spectroscopic properties of its iron–sulfur cluster and the unique ligand swapping ability of two cysteine ligands to the [Fe2S2] cluster. Although the physiological role of this ferredoxin remains unclear, a strong and specific interaction of Cp2FeFd with the molybdenum-iron protein of
Crystal structure of human ferredoxin-1 (FDX1).
|Locus||Chr. 11 q22.3|
Adrenodoxin (adrenal ferredoxin; InterPro: IPR001055), putidaredoxin, and terpredoxin make up a family of soluble Fe2S2 proteins that act as single electron carriers, mainly found in eukaryotic mitochondria and Proteobacteria. The human variant of adrenodoxin is referred to as ferredoxin-1 and ferredoxin-2. In mitochondrial monooxygenase systems, adrenodoxin transfers an electron from NADPH:adrenodoxin reductase to membrane-bound cytochrome P450. In bacteria, putidaredoxin and terpredoxin transfer electrons between corresponding NADH-dependent ferredoxin reductases and soluble P450s. The exact functions of other members of this family are not known, although Escherichia coli Fdx is shown to be involved in biogenesis of Fe–S clusters. Despite low sequence similarity between adrenodoxin-type and plant-type ferredoxins, the two classes have a similar folding topology.
Ferredoxin-1 in humans participates in the synthesis of thyroid hormones. It also transfers electrons from adrenodoxin reductase to CYP11A1, a CYP450 enzyme responsible for cholesterol side chain cleavage. FDX-1 has the capability to bind to metals and proteins. Ferredoxin-2 participates in heme A and iron–sulphur protein synthesis.
Fe4S4 and Fe3S4 ferredoxinsEdit
The [Fe4S4] ferredoxins may be further subdivided into low-potential (bacterial-type) and high-potential (HiPIP) ferredoxins.
Low- and high-potential ferredoxins are related by the following redox scheme:
The formal oxidation numbers of the iron ions can be [2Fe3+, 2Fe2+] or [1Fe3+, 3Fe2+] in low-potential ferredoxins. The oxidation numbers of the iron ions in high-potential ferredoxins can be [3Fe3+, 1Fe2+] or [2Fe3+, 2Fe2+].
|3Fe-4S binding domain|
Structural representation of an Fe3S4 ferredoxin.
|SCOPe||5fd1 / SUPFAM|
A group of Fe4S4 ferredoxins, originally found in bacteria, has been termed "bacterial-type". Bacterial-type ferredoxins may in turn be subdivided into further groups, based on their sequence properties. Most contain at least one conserved domain, including four cysteine residues that bind to a [Fe4S4] cluster. In Pyrococcus furiosus Fe4S4 ferredoxin, one of the conserved Cys residues is substituted with aspartic acid.
During the evolution of bacterial-type ferredoxins, intrasequence gene duplication, transposition and fusion events occurred, resulting in the appearance of proteins with multiple iron–sulfur centers. In some bacterial ferredoxins, one of the duplicated domains has lost one or more of the four conserved Cys residues. These domains have either lost their iron–sulfur binding property or bind to a [Fe3S4] cluster instead of a [Fe4S4] cluster and dicluster-type.
3-D structures are known for a number of monocluster and dicluster bacterial-type ferredoxins. The fold belongs to the α+β class, with 2-7 α-helices and four β-strands forming a barrel-like structure, and an extruded loop containing three "proximal" Cys ligands of the iron–sulfur cluster.
High-potential iron–sulfur proteinsEdit
High potential iron–sulfur proteins (HiPIPs) form a unique family of Fe4S4 ferredoxins that function in anaerobic electron transport chains. Some HiPIPs have a redox potential higher than any other known iron–sulfur protein (e.g., HiPIP from Rhodopila globiformis has a redox potential of ca. 450 mV). Several HiPIPs have so far been characterized structurally, their folds belonging to the α+β class. As in other bacterial ferredoxins, the [Fe4S4] unit forms a cubane-type cluster and is ligated to the protein via four Cys residues.
Human proteins from ferredoxin familyEdit
Evolution of ferredoxinsEdit
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