The disulfide bond isomerase DsbC is activated by an immunoglobulin-fold thiol oxidoreductase: crystal structure of the DsbC-DsbDα complex

• Published in: The EMBO journal Vol. 21; no. 18; pp. 4774 - 4784
• Main Authors: Haebel, Peter W., Goldstone, David, Katzen, Federico, Beckwith, Jon, Metcalf, Peter
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 16.09.2002; Oxford University Press
• Subjects: disulfide bond isomerase DsbC; electron transporter DsbD; oxidative protein folding; reaction intermediate; thiol oxidoreductase
• ISSN: 0261-4189; 1460-2075
• DOI: 10.1093/emboj/cdf489

The Escherichia coli disulfide bond isomerase DsbC rearranges incorrect disulfide bonds during oxidative protein folding. It is specifically activated by the periplasmic N‐terminal domain (DsbDα) of the transmembrane electron transporter DsbD. An intermediate of the electron transport reaction was trapped, yielding a covalent DsbC–DsbDα complex. The 2.3 Å crystal structure of the complex shows for the first time the specific interactions between two thiol oxidoreductases. DsbDα is a novel thiol oxidoreductase with the active site cysteines embedded in an immunoglobulin fold. It binds into the central cleft of the V‐shaped DsbC dimer, which assumes a closed conformation on complex formation. Comparison of the complex with oxidized DsbDα reveals major conformational changes in a cap structure that regulates the accessibility of the DsbDα active site. Our results explain how DsbC is selectively activated by DsbD using electrons derived from the cytoplasm.