Structure and mechanisms of the DsbB-DsbA disulfide bond generation machine

Kenji Inaba, Koreaki Ito

Research output: Contribution to journalReview articlepeer-review

71 Citations (Scopus)


All organisms possess specific cellular machinery that introduces disulfide bonds into proteins newly synthesized and transported out of the cytosol. In E. coli, the membrane-integrated DsbB protein cooperates with ubiquinone to generate a disulfide bond, which is transferred to DsbA, a periplasmic dithiol oxido-reductase that serves as the direct disulfide bond donor to proteins folding oxidatively in this compartment. Despite the extensive accumulation of knowledge on this oxidation system, molecular details of the DsbB reaction mechanisms had been controversial due partly to the lack of structural information until our recent determination of the crystal structure of a DsbA-DsbB-ubiquinone complex. In this review we discuss the structural and chemical nature of reaction intermediates in the DsbB catalysis and the illuminated molecular mechanisms that account for the de novo formation of a disulfide bond and its donation to DsbA. It is suggested that DsbB gains the ability to oxidize its specific substrate, DsbA, having very high redox potential, by undergoing a DsbA-induced rearrangement of cysteine residues. One of the DsbB cysteines that are now reduced then interacts with ubiquinone to form a charge transfer complex, leading to the regeneration of a disulfide at the DsbB active site, and the cycle can begin anew.

Original languageEnglish
Pages (from-to)520-529
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number4
Publication statusPublished - 2008 Apr


  • Crystal structure
  • Disulfide bond generation
  • DsbA
  • DsbB
  • Membrane-bound oxidase
  • Menaquinone
  • Ubiquinone


Dive into the research topics of 'Structure and mechanisms of the DsbB-DsbA disulfide bond generation machine'. Together they form a unique fingerprint.

Cite this