Crystal structure of enterotoxigenic Escherichia coli colonization factor CS6 reveals a novel type of functional assembly

Authors

  • Saumendra P. Roy,

    1. Department of Molecular Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
    2. Department of Chemistry, University of Turku, Turku, Finland
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    • These authors contributed equally to this work.
  • Mohammad M. Rahman,

    1. Department of Chemistry, University of Turku, Turku, Finland
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    • These authors contributed equally to this work.
  • Xiao Di Yu,

    1. Department of Molecular Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
    Current affiliation:
    1. The F. M. Kirby Neurobiology Center, Boston Children's Hospital, Boston, MA, USA
    2. Department of Neurology, Harvard Medical School, Boston, MA, USA
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    • These authors contributed equally to this work.
  • Minna Tuittila,

    1. Department of Chemistry, University of Turku, Turku, Finland
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    • These authors contributed equally to this work.
  • Stefan D. Knight,

    1. Department of Molecular Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
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  • Anton V. Zavialov

    Corresponding author
    1. Department of Chemistry, University of Turku, Turku, Finland
    • Department of Molecular Biology, Uppsala BioCenter, Swedish University of Agricultural Sciences, Uppsala, Sweden
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For correspondence. E-mail anton.zavialov@molbio.slu.se or anton.zavialov@utu.fi; Tel. (+46) 18 47 14 047; Fax (+46) 18 53 69 71.

Summary

Coli surface antigen 6 (CS6) is a widely expressed enterotoxigenic Escherichia coli (ETEC) colonization factor that mediates bacterial attachment to the small intestinal epithelium. CS6 is a polymer of two protein subunits CssA and CssB, which are secreted and assembled on the cell surface via the CssC/CssD chaperone usher (CU) pathway. Here, we present an atomic resolution model for the structure of CS6 based on the results of X-ray crystallographic, spectroscopic and biochemical studies, and suggest a mechanism for CS6-mediated adhesion. We show that the CssA and CssB subunits are assembled alternately in linear fibres by the principle of donor strand complementation. This type of fibre assembly is novel for CU assembled adhesins. We also show that both subunits in the fibre bind to receptors on epithelial cells, and that CssB, but not CssA, specifically recognizes the extracellular matrix protein fibronectin. Taken together, structural and functional results suggest that CS6 is an adhesive organelle of a novel type, a hetero-polyadhesin that is capable of polyvalent attachment to different receptors.

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