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The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)1538-1549
Number of pages12
JournalJournal of Biological Chemistry
Volume292
Issue number5
DOIs
DateAccepted/In press - 5 Dec 2016
DatePublished (current) - 3 Feb 2017

Abstract

Adherence of bacteria to biotic or abiotic surfaces is a prerequisite for host colonization and represents an important step in microbial pathogenicity. This attachment is facilitated by bacterial adhesins at the cell surface. Because of their size and often elaborate multidomain architectures, these polypeptides represent challenging targets for detailed structural and functional characterization. The multifunctional fibrillar adhesin CshA, which mediates binding to both host molecules and other microorganisms, is an important determinant of colonization by Streptococcus gordonii, an oral commensal and opportunistic pathogen of animals and humans. CshA binds the high-molecularweight glycoprotein fibronectin (Fn) via an N-terminal non-repetitive region, and this protein-protein interaction has been proposed to promote S. gordonii colonization at multiple sites within the host. However, the molecular details of how these two proteins interact have yet to be established. Here we present a structural description of the Fn binding N-terminal region of CshA, derived from a combination of X-ray crystallography, small angle X-ray scattering, and complementary biophysical methods. In vitro binding studies support a previously unreported two-state "catch-clamp" mechanism of Fn binding by CshA, in which the disordered N-terminal domain of CshA acts to "catch" Fn, via formation of a rapidly assembled but also readily dissociable pre-complex, enabling its neighboring ligand binding domain to tightly clamp the two polypeptides together. This study presents a new paradigm for target binding by a bacterial adhesin, the identification of which will inform future efforts toward the development of anti-adhesive agents that target S. gordonii and related streptococci.

    Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio

    Research areas

  • Adhesin, intrinsically disordered protein, X-ray crystallography, SAXS, bacterial pathogenesis, microbiology

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via ASBMB at http://www.jbc.org/content/early/2016/12/05/jbc.M116.760975. Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 7 MB, PDF document

  • Full-text PDF (final published version)

    Rights statement: This is the final published version of the article (version of record). It first appeared online via ASBMB at http://www.jbc.org/content/292/5/1538.full . Please refer to any applicable terms of use of the publisher.

    Final published version, 2 MB, PDF document

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