Open AccessAn in vivo pathway for disulfide bond isomerization in Escherichia coli
Author(s) -
Arne Rietsch,
Dominique Belin,
Nancy L. Martin,
Jonathan Beckwith
Publication year - 1996
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.93.23.13048
Subject(s) - protein disulfide isomerase , dsba , periplasmic space , thioredoxin , isomerase , biochemistry , dithiothreitol , chemistry , pyrococcus furiosus , isomerization , disulfide linkage , protein folding , foldase , mutant , escherichia coli , cysteine , enzyme , gene , groel , archaea , catalysis
Biochemical studies have shown that the periplasmic protein disulfide oxidoreductase DsbC can isomerize aberrant disulfide bonds. Here we present the first evidence for anin vivo role of DsbC in disulfide bond isomerization. Furthermore, our data suggest that the enzymes DsbA and DsbC play distinct roles in the cell in disulfide bond formation and isomerization, respectively. We have shown that mutants indsbC display a defect in disulfide bond formation specific for proteins with multiple disulfide bonds. The defect can be complemented by the addition of reduced dithiothreitol to the medium, suggesting that absence of DsbC results in accumulation of misoxidized proteins. Mutations in thedipZ andtrxA genes have similar phenotypes. We propose that DipZ, a cytoplasmic membrane protein with a thioredoxin-like domain, and thioredoxin, the product of thetrxA gene, are components of a pathway for maintaining DsbC active as a protein disulfide bond isomerase.