Diversity of the Dsb (disulfide bond) oxidative protein folding pathways in microbial world

The introduction of structural disulfide bonds is crucial to the stability and activity of many extra-cytoplasmic proteins. The disulfide bond formation is a rate-limiting step in the folding process of a protein. However, most microorganisms encode a machinery to catalyse this oxidative protein folding step. In prototypic Escherichia coli oxidative pathway, the introduction of disulfide bridges into folding proteins is mediated by the thioredoxin family members - Dsb system proteins. Correct oxidative protein folding in the E. coli envelope depends on both EcDsbA and EcDsbB. Periplasmic oxidoreductase EcDsbA is a key disulfide bond formation catalyst, which is maintained in its active form by membrane-bound protein EcDsbB. To date, over 300 EcDsbA homologues from different bacterial organisms have been identified. Nevertheless, the structure, function and interactions of EcDsbA still remain the best studied. The rapidly expanding number of sequenced bacterial genomes has revealed dramatic differences between the model E. coli oxidative pathway and the pathway in other microorganisms. In this article, we review current knowledge about EcDsbA and focus on the diversity of the disulfide bond generation pathways functioning in the microbial world.