Crystal structure of the DsbA protein required for disulphide bond formation in vivo

Abstract

PROTEINS that contain disulphide bonds are often slow to fold in vitro because the oxidation and correct pairing of the cysteine residues is rate limiting1,2. The folding of such proteins is greatly accelerated in Escherichia coli by DsbA3,4, but the mechanism of this rate enhancement is not well understood. Here we report the crystal structure of oxidized DsbA and show that it resembles closely the ubiquitous redox protein thioredoxin5, despite very low sequence similarity. An important difference, however, is the presence of another domain which forms a cap over the thioredoxin-like active site of DsbA. The redox–active disulphide bond, which is responsible for the oxidation of substrates, is thus at a domain interface and is surrounded by grooves and exposed hydrophobic side chains. These features suggest that DsbA might act by binding to partially folded polypeptide chains before oxidation of cysteine residues.