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

Lookup NU author(s): Professor Paul RaceORCiD

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Abstract

© 2017 by The American Society for Biochemistry and Molecular Biology, Inc. 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.

Publication metadata

Author(s): Back CR, Sztukowska MN, Till M, Lamont RJ, Jenkinson HF, Nobbs AH, Race PR

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2017

Volume: 292

Issue: 5

Pages: 1538-1549

Print publication date: 03/02/2017

Online publication date: 05/12/2016

Acceptance date: 02/04/2016

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology Inc.

URL: https://doi.org/10.1074/jbc.M116.760975

DOI: 10.1074/jbc.M116.760975

PubMed id: 27920201

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