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Lipoprotein rotamase A

(Redirected from Draft:Lipoprotein rotamase A (SlrA))

Lipoprotein rotamase A (SlrA), also known as peptidyl prolyl isomerase A (PpiA), functions as a molecular chaperone that operates within the Streptococcus pneumoniae cell membrane-cell wall interface as well as outside the bacteria.[1][2][3] SlrA shares homology with the cyclophilin-type peptidyl-prolyl isomerases (PPIases).[4] PPIases accelerate the folding of proteins by catalyzing the cis-trans isomer conversions of peptide bonds in the amino acid proline.[5]

Structure

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AlphaFold predicted structure of SlrA

SlrA is a 29kDa,[6][7] 267-amino acid long membrane-bound lipoprotein.[1] It is encoded by the S. pneumoniae gene, SP_0771, located at position 729,840–730,643 on the complementary strand.[7] The structure of SlrA is predicted to contain an eight-strand β-bundle and two associated α-helices, similar to the PPIase domains of cyclophilins.[8][9][10]

Lipidated forms of SlrA occur in all sequenced streptococcal genomes with the homologs sharing 60-70% amino acid sequence identity.[4] SlrA also shares homology with other Gram-positive cyclophilins such as the membrane-bound PpiA in Lactococcus lactis.[11]

Function

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As a PPIase, SlrA functions at the rate-limiting step of protein folding of secreted proteins. The identity of the proteins folded by SlrA and SlrA homologs are still under investigation, but the roles of these proteins can be hypothesized based on the phenotypes observed in mutants without SlrA. The SlrA homologs in Streptococcus mutans and Streptococcus gordonii, PpiA, also display anti-phagocytic activity in their respective bacteria.[12][13] SlrA has been implicated in S. pneumoniae colonization, competence, cell wall integrity, and adhesion to human cells derived from the upper and lower respiratory tract.[7] It is hypothesized that SlrA acts as a protein-folding chaperone for client proteins involved in those key processes. Additionally, SlrA has been shown to indirectly contribute to S. pneumoniae anti-phagocytic activity [14]

References

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  1. ^ a b Sun, X (October 2011). "Proteomic analysis of membrane proteins from Streptococcus pneumoniae with multiple separation methods plus high accuracy mass spectrometry". OMICS. 15 (10): 683–694. doi:10.1089/omi.2010.0133. PMID 21978396.
  2. ^ Choi, CW (April 2012). "Analysis of Streptococcus pneumoniae secreted antigens by immuno-proteomic approach". Diagnostic Microbiology and Infectious Disease. 72 (4): 318–327. doi:10.1016/j.diagmicrobio.2011.12.013. PMID 22306351.
  3. ^ Pribyl, T (February 2014). "Influence of impaired lipoprotein biogenesis on surface and exoproteome of Streptococcus pneumoniae". Journal of Proteome Research. 13 (2): 650–667. doi:10.1021/pr400768v. PMID 24387739.
  4. ^ a b Adrian, T (July 2004). "Development of antibodies against pneumococcal proteins alpha-enolase, immunoglobulin A1 protease, streptococcal lipoprotein rotamase A, and putative proteinase maturation protein A in relation to pneumococcal carriage and Otitis Media". Vaccine. 22 (21–22): 2737–2742. doi:10.1016/j.vaccine.2004.01.042. PMID 15246605.
  5. ^ Dunyak, Bryan (July 2016). "Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds". Journal of Medicinal Chemistry. 59 (21): 9622–9644. doi:10.1021/acs.jmedchem.6b00411. PMC 5501181. PMID 27409354.
  6. ^ Khandavilli, Suneeta (February 2008). "Maturation of Streptococcus pneumoniae lipoproteins by a type II signal peptidase is required for ABC transporter function and full virulence". Molecular Microbiology. 67 (3): 541–557. doi:10.1111/j.1365-2958.2007.06065.x. PMC 2228790. PMID 18086214.
  7. ^ a b c George, Jada (February 2024). "Streptococcus pneumoniae secretion chaperones PrsA, SlrA, and HtrA are required for competence, antibiotic resistance, colonization, and invasive disease". Infection and Immunity. 92 (2): e0049023. doi:10.1128/iai.00490-23. PMC 10863415. PMID 38226817.
  8. ^ Flaherty, Patrick (12 October 2011). "20: Peptidyl Prolyl Isomerase Inhibitors". Annual Reports in Medicinal Chemistry. Vol. 47. Cambridge, Massachusetts: Academic Press Inc. (Verlag). pp. 337–339. ISBN 9780123860248.
  9. ^ Jumper, J (August 2021). "Highly accurate protein structure prediction with AlphaFold". Nature. 596 (7873): 583–589. Bibcode:2021Natur.596..583J. doi:10.1038/s41586-021-03819-2. PMC 8371605. PMID 34265844.
  10. ^ Varadi, M (January 2022). "AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models". Nucleic Acids Research. 50 (D1): D439–D444. doi:10.1093/nar/gkab1061. PMC 8728224. PMID 34791371.
  11. ^ Trémillon, N (March 2012). "PpiA, a surface PPIase of the cyclophilin family in Lactococcus lactis". PLOS ONE. 7 (3): e33516. Bibcode:2012PLoSO...733516T. doi:10.1371/journal.pone.0033516. PMC 3307742. PMID 22442694.
  12. ^ Cho, K (October 2013). "Involvement of lipoprotein PpiA of Streptococcus gordonii in evasion of phagocytosis by macrophages". Molecular Oral Microbiology. 28 (5): 379–391. doi:10.1111/omi.12031. PMID 23734737.
  13. ^ Mukouhara, T (December 2011). "Surface lipoprotein PpiA of Streptococcus mutans suppresses scavenger receptor MARCO-dependent phagocytosis by macrophages". Infection and Immunity. 79 (12): 4933–4940. doi:10.1128/IAI.05693-11. PMC 3232644. PMID 21986627.
  14. ^ Hermans, PW (January 2006). "The streptococcal lipoprotein rotamase A (SlrA) is a functional peptidyl-prolyl isomerase involved in pneumococcal colonization". Journal of Biological Chemistry. 281 (2): 968–976. doi:10.1128/iai.00490-23. PMC 10863415. PMID 38226817.
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