In vivo oxidative protein folding can be facilitated by oxidation-reduction cycling

Mol Microbiol. 2010 Jan;75(1):13-28. doi: 10.1111/j.1365-2958.2009.06952.x. Epub 2009 Dec 3.


Current dogma dictates that bacterial proteins with misoxidized disulfide bonds are shuffled into correctly oxidized states by DsbC. There are two proposed mechanisms for DsbC activity. The first involves a DsbC-only model of substrate disulfide rearrangement. The second invokes cycles of reduction and oxidation of substrate disulfide bonds by DsbC and DsbA respectively. Here, we addressed whether the second mechanism is important in vivo by identifying whether a periplasmic reductase could complement DsbC. We screened for naturally occurring periplasmic reductases in Bacteroides fragilis, a bacterium chosen because we predicted it encodes reductases and has a reducing periplasm. We found that the B. fragilis periplasmic protein TrxP has a thioredoxin fold with an extended N-terminal region; that it is a very active reductase but a poor isomerase; and that it fully complements dsbC. These results provide direct in vivo evidence that correctly folded protein is achievable via cycles of oxidation and reduction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteroides fragilis / chemistry
  • Bacteroides fragilis / enzymology*
  • Bacteroides fragilis / genetics
  • Crystallography, X-Ray
  • Disulfides / metabolism
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Gene Deletion
  • Genetic Complementation Test
  • Models, Biological
  • Models, Molecular
  • Oxidation-Reduction
  • Oxidoreductases / chemistry
  • Oxidoreductases / genetics
  • Oxidoreductases / metabolism*
  • Periplasmic Proteins / chemistry
  • Periplasmic Proteins / genetics
  • Periplasmic Proteins / metabolism*
  • Protein Disulfide-Isomerases / chemistry*
  • Protein Disulfide-Isomerases / genetics
  • Protein Disulfide-Isomerases / metabolism*
  • Protein Folding*
  • Protein Structure, Tertiary


  • Disulfides
  • Escherichia coli Proteins
  • Periplasmic Proteins
  • Oxidoreductases
  • Protein Disulfide-Isomerases
  • dsbC protein, E coli

Associated data

  • PDB/3HXS
  • PDB/3HYP