A Bucket Brigade

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Science  15 Dec 2000:
Vol. 290, Issue 5499, pp. 2033-2035
DOI: 10.1126/science.290.5499.2033e

In Escherichia coli, disulfide bond formation occurs in the periplasm under the control of the Dsb system. The cytoplasmic membrane protein, DsbD mediates electron transfer from the cytoplasm to the periplasm by providing reducing equivalents that then are used by the periplasmic protein DsbC to catalyze the rearrangement of disulfide bonds.

Katzen and Beckwith split DsbD into its three structural domains—an amino terminal periplasmic domain, a transmembrane domain, and a carboxyl terminal domain—and showed that electrons are transferred directly from cytoplasmic thioredoxin to a pair of cysteine residues in the transmembrane domain of DsbD. In a cascade of disulfide bond reduction and formation, the reducing equivalents are then shuttled via more cysteines through the thioredoxin-like carboxyl terminal domain into the amino terminal catalytic domain. From here the electrons are transferred directly to periplasmic substrates such as DsbC. Krupp et al. have used cysteine substitution mutants to trap mixed disulfide intermediates between intact DsbD and both thioredoxin and DsbC, delineating the same pathway. One outstanding question is how the cysteine pair in the transmembrane domain of DsbD becomes accessible sequentially to cytoplasmic thioredoxin and to the periplasm. — VV

Cell103, 769 (2000); J. Biol. Chem., in press.

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