Disulfide Chains

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Science  07 Jun 2002:
Vol. 296, Issue 5574, pp. 1767
DOI: 10.1126/science.296.5574.1767c

In Escherichia coli, the periplasmic protein DsbA catalyzes disulfide bond formation in newly synthesized proteins that have been exported across the cytoplasmic membrane. (The periplasm and outer environs can be somewhat harsh, and the structural support of disulfide links is critical for protein stability and function.) The cytoplasmic protein DsbB maintains DsbA in the oxidized state by accepting electrons from reduced DsbA and transferring them to a membrane-embedded quinone. The activity of DsbB depends on two disulfide bonds, Cys41-Cys44 and Cys104-Cys130, located in the first and second periplasmic loops, respectively.

Two groups show that disulfide transfer from DsbB to DsbA is not as simple as might have been supposed. Kadokura and Beckwith reconstituted DsbB activity by expressing the two halves of DsbB, each containing one of the disulfide bonds. They detected a ternary complex (of the two halves plus DsbA) that appears to represent an intermediate in the electron transfer process. The complex contains an interprotein disulfide between Cys30 of DsbA and Cys104 of DsbB and an interdomain disulfide between Cys130 and Cys41 of DsbB. This coordinated transfer may be required to prevent the back reaction, which would regenerate reduced DsbA; that is, after formation of the interprotein disulfide, Cys130 may be positioned to react readily with the Cys41-Cys44 bond. Inaba and Ito find that DsbB is intrinsically more reducing than DsbA with redox potentials of −0.21 V for Cys41-Cys44 and −0.25 V for Cys104-Cys130, yet only −0.12 V for the DsbA pair Cys30-Cys33. They suggest that the oxidizing power of ubiquinone (+0.11 V) may drive the reaction, with DsbB serving as a regulatory bottleneck. — VV

EMBO J.21, 2354; 2646 (2002).

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