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Gene Review

dsbA  -  periplasmic protein disulfide isomerase I

Escherichia coli str. K-12 substr. MG1655

Synonyms: ECK3852, JW3832, dsf, iarA, ppfA
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Disease relevance of dsbA

  • We describe a mutation (dsbA) that renders Escherichia coli severely defective in disulfide bond formation [1].
  • In a previous work where genes specific to N. meningitidis and not present in the other pathogenic Neisseria were isolated, a meningococcus-specific dsbA gene was brought to light (Tinsley, C. R., and Nassif, X. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 11109-11114) [2].
  • A search of available genome data revealed that the meningococcus contains three dsbA genes encoding proteins with different predicted subcellular locations, i.e. a soluble periplasmic enzyme and two membrane-bound lipoproteins [2].
  • An Erwinia chrysanthemi gene able to complement an Escherichia coli dsbA mutation has been cloned and sequenced [3].

High impact information on dsbA

  • The dsbA gene codes for a 21,000 Mr periplasmic protein containing the sequence cys-pro-his-cys, which resembles the active sites of certain disulfide oxidoreductases [1].
  • A search for extragenic mutations able to compensate for the lack of dsbA function in vivo led us to the identification of a new gene, designated dsbD [4].
  • The finding that overexpression of DsbD leads to a Dsb- phenotype, very similar to that exhibited by dsbA null mutants, is in good agreement with such a model [4].
  • The wild-type counterpart of this gene (named ppfA) has been sequenced and shown to encode a periplasmic protein with a pair of potentially redox-active cysteine residues [5].
  • In contrast, the inefficiently formed disulfide bonds in the dsbA-disrupted cells, and the more efficiently formed disulfide bonds in the same strain in the presence of oxidized glutathione were mostly in the correct form [6].

Chemical compound and disease context of dsbA


Biological context of dsbA

  • These phenotypes resemble the phenotype of bacteria carrying either a null mutation in the dsbA gene or the double mutation dsbA dsbB [10].
  • The dsbC gene introduced on a multicopy plasmid in a dsbA mutant was only partially able to restore EGZ secretion, indicating that even if DsbA and DsbC possess disulphide oxydoreductase activity, they are not completely interchangeable [3].
  • Previous studies with Escherichia coli demonstrated that dsbA is part of a two-gene operon that includes an uncharacterized, upstream gene, yihE, that is positively regulated via the Cpx stress response pathway [11].
  • While export of the cystein-less CtxB passenger was independent of the dsbA genotype, the native CtxB passenger was properly translocated across the outer membrane only in the dsbA mutant background [8].
  • The mutation was localized by conjugation, transduction, and Southern blotting experiments to the dsbA gene at minute 87 on the E. coli chromosome and was complemented by the wild-type allele [12].

Anatomical context of dsbA


Associations of dsbA with chemical compounds

  • Since the defective phenotype was similar to that of the spa32 mutant of S. flexneri and the Spa32 sequence possessed two Cys residues, the effect of dsbA mutation of the folding structure of Spa32 under reducing conditions and on the surface expression of Spa32 was investigated [13].
  • This DsbG defect could be rescued by addition to the growth medium of either oxidized dithiothreitol or cystine, or by overexpression of the dsbA or dsbB genes [14].
  • The analysis of structure-function relationships of PDI and dsbA have indicated that these thiol-disulfide oxidoreductases act as protein oxidants to facilitate the formation of disulfides during the folding process [15].
  • A dsbA/chloramphenicol acetylase construct was then used to disrupt the wild-type gene of S. typhi [16].

Other interactions of dsbA

  • To investigate the DsbA-DsbB catalytic system, we performed an in vivo selection for chromosomal dsbA and dsbB mutants [17].
  • Expression of scFv- or V(HH)-C-IgAP hybrids in E. coli dsbA or fkpA mutant cells reveals that these periplasmic protein chaperones fold these N-domains before their translocation across the OM [18].
  • After fusion to pelB, dsbA or ompT signal peptides no recombinant product could be obtained in the periplasm using the T7 promoter [19].
  • We observed a lack of DsbA, glucose-1-phosphatase and flagellin in the dsbA-null mutant, which explains two of the observed phenotypes [16].

Analytical, diagnostic and therapeutic context of dsbA

  • Sequence analysis showed that the TnphoA insertion was located in the dsbA gene coding for a periplasmic protein required for disulfide bond formation [9].


  1. Identification of a protein required for disulfide bond formation in vivo. Bardwell, J.C., McGovern, K., Beckwith, J. Cell (1991) [Pubmed]
  2. Three homologues, including two membrane-bound proteins, of the disulfide oxidoreductase DsbA in Neisseria meningitidis: effects on bacterial growth and biogenesis of functional type IV pili. Tinsley, C.R., Voulhoux, R., Beretti, J.L., Tommassen, J., Nassif, X. J. Biol. Chem. (2004) [Pubmed]
  3. Differential effect of dsbA and dsbC mutations on extracellular enzyme secretion in Erwinia chrysanthemi. Shevchik, V.E., Bortoli-German, I., Robert-Baudouy, J., Robinet, S., Barras, F., Condemine, G. Mol. Microbiol. (1995) [Pubmed]
  4. Identification and characterization of a new disulfide isomerase-like protein (DsbD) in Escherichia coli. Missiakas, D., Schwager, F., Raina, S. EMBO J. (1995) [Pubmed]
  5. Identification and characterization of an Escherichia coli gene required for the formation of correctly folded alkaline phosphatase, a periplasmic enzyme. Kamitani, S., Akiyama, Y., Ito, K. EMBO J. (1992) [Pubmed]
  6. Differential in vivo roles played by DsbA and DsbC in the formation of protein disulfide bonds. Sone, M., Akiyama, Y., Ito, K. J. Biol. Chem. (1997) [Pubmed]
  7. Human protein disulfide isomerase functionally complements a dsbA mutation and enhances the yield of pectate lyase C in Escherichia coli. Humphreys, D.P., Weir, N., Mountain, A., Lund, P.A. J. Biol. Chem. (1995) [Pubmed]
  8. Absence of periplasmic DsbA oxidoreductase facilitates export of cysteine-containing passenger proteins to the Escherichia coli cell surface via the Iga beta autotransporter pathway. Jose, J., Krämer, J., Klauser, T., Pohlner, J., Meyer, T.F. Gene (1996) [Pubmed]
  9. Insertional inactivation of dsbA produces sensitivity to cadmium and zinc in Escherichia coli. Rensing, C., Mitra, B., Rosen, B.P. J. Bacteriol. (1997) [Pubmed]
  10. Identification and characterization of the Escherichia coli gene dsbB, whose product is involved in the formation of disulfide bonds in vivo. Missiakas, D., Georgopoulos, C., Raina, S. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  11. Salmonella enterica serovar typhimurium rdoA is growth phase regulated and involved in relaying Cpx-induced signals. Suntharalingam, P., Spencer, H., Gallant, C.V., Martin, N.L. J. Bacteriol. (2003) [Pubmed]
  12. An essential role for DsbA in cytochrome c synthesis and formate-dependent nitrite reduction by Escherichia coli K-12. Metheringham, R., Griffiths, L., Crooke, H., Forsythe, S., Cole, J. Arch. Microbiol. (1995) [Pubmed]
  13. Disulfide oxidoreductase activity of Shigella flexneri is required for release of Ipa proteins and invasion of epithelial cells. Watarai, M., Tobe, T., Yoshikawa, M., Sasakawa, C. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  14. A new Escherichia coli gene, dsbG, encodes a periplasmic protein involved in disulphide bond formation, required for recycling DsbA/DsbB and DsbC redox proteins. Andersen, C.L., Matthey-Dupraz, A., Missiakas, D., Raina, S. Mol. Microbiol. (1997) [Pubmed]
  15. Enzymatic catalysis of disulfide formation. Noiva, R. Protein Expr. Purif. (1994) [Pubmed]
  16. A proteomic approach to study Salmonella typhi periplasmic proteins altered by a lack of the DsbA thiol: disulfide isomerase. Agudo, D., Mendoza, M.T., Castañares, C., Nombela, C., Rotger, R. Proteomics (2004) [Pubmed]
  17. Mutational analysis of the disulfide catalysts DsbA and DsbB. Tan, J., Lu, Y., Bardwell, J.C. J. Bacteriol. (2005) [Pubmed]
  18. Structural tolerance of bacterial autotransporters for folded passenger protein domains. Veiga, E., de Lorenzo, V., Fernández, L.A. Mol. Microbiol. (2004) [Pubmed]
  19. A novel fusion protein system for the production of native human pepsinogen in the bacterial periplasm. Malik, A., Rudolph, R., Söhling, B. Protein Expr. Purif. (2006) [Pubmed]
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