Crystal structure of DsbDγ reveals the mechanism of redox potential shift and substrate specificity

Abstract

The Escherichia coli transmembrane protein DsbD transfers electrons from the cytoplasm to the periplasm through a cascade of thiol-disulfide exchange reactions. In this process, the C-terminal periplasmic domain of DsbD (DsbDγ) shuttles the reducing potential from the membrane domain (DsbDβ) to the N-terminal periplasmic domain (DsbDα). The crystal structure of DsbDγ determined at 1.9 ? resolution reveals that the domain has a thioredoxin fold with an extended N-terminal stretch. In comparison to thioredoxin, the DsbDγ structure exhibits the stabilized active site conformation and the extended active site α2 helix that explain the domain's substrate specificity and the redox potential shift, respectively. The hypothetical model of the DsbDγ:DsbDα complex based on the DsbDγ structure and previous structural studies indicates that the conserved hydrophobic residue in the C-X-X-C motif of DsbDγ may be important in the specific recognition of DsbDα.