The multidrug resistance IncA/C transferable plasmid encodes a novel domain swapped dimeric protein disulfide isomerase

Premkumar, Lakshmanane, Kurth, Fabian, Neyer, Simon, Schembri, Mark A. and Martin, Jennifer L. (2013) The multidrug resistance IncA/C transferable plasmid encodes a novel domain swapped dimeric protein disulfide isomerase. Journal of Biological Chemistry, Papers in Press 5: 1-24. doi:10.1074/jbc.M113.516898

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Author Premkumar, Lakshmanane
Kurth, Fabian
Neyer, Simon
Schembri, Mark A.
Martin, Jennifer L.
Title The multidrug resistance IncA/C transferable plasmid encodes a novel domain swapped dimeric protein disulfide isomerase
Journal name Journal of Biological Chemistry   Check publisher's open access policy
ISSN 0021-9258
Publication date 2013-12-05
Year available 2014
Sub-type Article (original research)
DOI 10.1074/jbc.M113.516898
Open Access Status File (Publisher version)
Volume Papers in Press
Issue 5
Start page 1
End page 24
Total pages 24
Place of publication Bethesda, MD, United States
Publisher American Society for Biochemistry and Molecular Biology
Language eng
Formatted abstract
Background: Bacterial IncA/C plasmids distribute antibiotic resistance genes and encode a conserved thioredoxin-fold protein (DsbP)

Results: DsbP shuffles incorrect disulfide bonds in misfolded proteins, and its structure diverges from previously characterized disulfide isomerases

Conclusion: Plasmid-encoded DsbP is a novel domain swapped protein disulfide isomerase

Significance: IIncA/C plasmids may encode this protein proofreading machinery to ensure horizontal gene transfer of antibiotic resistance genes

The multidrug resistance-encoding IncA/C conjugative plasmids disseminate antibiotic resistance genes among clinically relevant enteric bacteria. A plasmid-encoded disulfide isomerase is associated with conjugation. Sequence analysis of several IncA/C plasmids and IncA/C related integrative and conjugative elements (ICE) from commensal and pathogenic bacteria identified a conserved DsbC/DsbG homolog (DsbP). The crystal structure of DsbP reveals an N-terminal domain, a linker region and a C-terminal catalytic domain. A DsbP homodimer is formed through domain-swapping of two DsbP N-terminal domains. The catalytic domain incorporates a thioredoxin fold with characteristic CXXC and cisPro motifs. Overall, the structure and redox properties of DsbP diverge from the Escherichia coli DsbC and DsbG disulfide isomerases. Specifically, the V-shaped dimer of DsbP is inverted compared to EcDsbC and EcDsbG. In addition, the redox potential of DsbP (-161 mV) is more reducing than EcDsbC (-130 mV) and EcDsbG (-126 mV). Other catalytic properties of DsbP more closely resemble those of EcDsbG than EcDsbC. These catalytic differences are in part a consequence of the unusual active site motif of DsbP (CAVC); substitution to the EcDsbC-like (CGYC) motif converts the catalytic properties to those of EcDsbC. Structural comparison of the 12 independent subunit structures of DsbP that we determined revealed that conformational changes in the linker region contribute to mobility of the catalytic domain, providing mechanistic insight into DsbP function. In summary, our data reveal that the conserved plasmid-encoded DsbP protein is a bona fide disulfide isomerase and suggest that a dedicated oxidative folding enzyme is important for conjugative plasmid transfer.
Keyword Multidrug resistance
Disulfide isomerase
Domain swapping
Bacterial conjugation
Horizontal gene transfer
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID FL0992138
Institutional Status UQ
Additional Notes Published online December 5, 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Chemistry and Molecular Biosciences
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
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Created: Sun, 08 Dec 2013, 16:57:20 EST by Prem Lakshmanane on behalf of Institute for Molecular Bioscience