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

Nature volume 365, pages 464–468 (1993)Cite this article

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.

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Author notes

  1. Jennifer L. Martin

    Present address: Centre for Drug Design & Development, University of Queensland, Brisbane, 4072, Australia

  2. James C. A. Bardwell

    Present address: Institut fur Biophysik und Physikalische Biochemie, Universitat Regensburg, 8400, Regensburg, Germany

Authors and Affiliations

  1. The Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, New York, 10021, USA

    Jennifer L. Martin & John Kuriyan

  2. Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, Massachusetts, 02115, USA

    James C. A. Bardwell

  3. Centre for Drug Design & Development, University of Queensland, Brisbane, 4072, Australia

    James C. A. Bardwell

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  1. Jennifer L. Martin
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  3. John Kuriyan
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Martin, J., Bardwell, J. & Kuriyan, J. Crystal structure of the DsbA protein required for disulphide bond formation in vivo. Nature 365, 464–468 (1993). https://doi.org/10.1038/365464a0

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