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Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli

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Abstract

THE Shiga toxin family, a group of cytotoxins associated with diarrhoeal diseases and the haemolytic uraemic syndrome, includes Shiga toxin from Shigella dysenteriae type 1 and verotoxins1 produced by enteropathogenic Escherichia coli. The family belongs to the A–B class of bacterial toxins, which includes the cholera toxin family, pertussis and diphtheria toxins. These toxins all have bipartite structures consisting of an enzymatic A subunit associated with a B oligomer which binds to specific cell-surface receptors, but their amino-acid sequences and pathogenic mechanisms differ. We have determined the crystal structure of the B oligomer of verotoxin-1 from E. coll. The structure unexpectedly resembles that of the B oligomer of the cholera toxin-like heat-labile enterotoxin fromE. coli2, despite the absence of detectable sequence similarity between these two proteins. This result implies a distant evolutionary relationship between the Shiga toxin and cholera toxin families. We suggest that the cell surface receptor-binding site lies in a cleft between adjacent subunits of the B pentamer, providing a potential target for drugs and vaccines to prevent toxin binding and effect.

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Authors and Affiliations

  1. Department of Medical Microbiology and Infectious Diseases, University of Alberta, Edmonton, Alberta, T6G 2H7, Canada

    Penelope E. Stein, Amechand Boodhoo & Randy J. Read

  2. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5G 1X5, Canada

    Gregory J. Tyrrell

  3. Departments of Microbiology,

    Gregory J. Tyrrell

  4. Medicine, University of Toronto, Toronto, Ontario, M5S 1A1, Canada

    James L. Brunton

Authors
  1. Penelope E. Stein
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  2. Amechand Boodhoo
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  3. Gregory J. Tyrrell
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  4. James L. Brunton
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  5. Randy J. Read
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Stein, P., Boodhoo, A., Tyrrell, G. et al. Crystal structure of the cell-binding B oligomer of verotoxin-1 from E. coli. Nature 355, 748–750 (1992). https://doi.org/10.1038/355748a0

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  • DOI: https://doi.org/10.1038/355748a0

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