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 enhanc
ement 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 importa
nt 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 expose
d hydrophobic side chains. These features suggest that DsbA might act
by binding to partially folded polypeptide chains before oxidation of
cysteine residues.