The disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD-independent manner.

TitleThe disulphide isomerase DsbC cooperates with the oxidase DsbA in a DsbD-independent manner.
Publication TypeJournal Article
Year of Publication2008
AuthorsVertommen, D., M. Depuydt, J. Pan, P. Leverrier, L. Knoops, J-P. Szikora, J. Messens, J. C. A. Bardwell, and J-F. Collet
JournalMol Microbiol
Volume67
Issue2
Pagination336-49
Date Published2008 Jan
Type of Articleredox
ISSN0950-382X
KeywordsCysteine, Disulfides, Escherichia coli, Escherichia coli Proteins, Gene Expression Regulation, Bacterial, Mass Spectrometry, Models, Molecular, Oligonucleotide Array Sequence Analysis, Oxidation-Reduction, Periplasmic Proteins, Phenotype, Protein Disulfide-Isomerases, Protein Folding, Sequence Analysis, Protein, Sequence Deletion, Tandem Mass Spectrometry
Abstract

In Escherichia coli, DsbA introduces disulphide bonds into secreted proteins. DsbA is recycled by DsbB, which generates disulphides from quinone reduction. DsbA is not known to have any proofreading activity and can form incorrect disulphides in proteins with multiple cysteines. These incorrect disulphides are thought to be corrected by a protein disulphide isomerase, DsbC, which is kept in the reduced and active configuration by DsbD. The DsbC/DsbD isomerization pathway is considered to be isolated from the DsbA/DsbB pathway. We show that the DsbC and DsbA pathways are more intimately connected than previously thought. dsbA(-)dsbC(-) mutants have a number of phenotypes not exhibited by either dsbA(-), dsbC(-) or dsbA(-)dsbD(-) mutations: they exhibit an increased permeability of the outer membrane, are resistant to the lambdoid phage Phi80, and are unable to assemble the maltoporin LamB. Using differential two-dimensional liquid chromatographic tandem mass spectrometry/mass spectrometry analysis, we estimated the abundance of about 130 secreted proteins in various dsb(-) strains. dsbA(-)dsbC(-) mutants exhibit unique changes at the protein level that are not exhibited by dsbA(-)dsbD(-) mutants. Our data indicate that DsbC can assist DsbA in a DsbD-independent manner to oxidatively fold envelope proteins. The view that DsbC's function is limited to the disulphide isomerization pathway should therefore be reinterpreted.

DOI10.1111/j.1365-2958.2007.06030.x
Alternate JournalMol. Microbiol.
PubMed ID18036138
PubMed Central IDPMC2614554
Grant ListR01 GM057039 / GM / NIGMS NIH HHS / United States
R01 GM057039-09 / GM / NIGMS NIH HHS / United States
R01 GM064662 / GM / NIGMS NIH HHS / United States
R01 GM064662-04 / GM / NIGMS NIH HHS / United States
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