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

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The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism. / Back, Catherine; Sztukowska, Maryta N; Till, Marisa; Lamont, Richard J; Jenkinson, Howard F; Nobbs, Angela; Race, Paul.

In: Journal of Biological Chemistry, Vol. 292, No. 5, 03.02.2017, p. 1538-1549.

Research output: Contribution to journalArticle

Harvard

Back, C, Sztukowska, MN, Till, M, Lamont, RJ, Jenkinson, HF, Nobbs, A & Race, P 2017, 'The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism', Journal of Biological Chemistry, vol. 292, no. 5, pp. 1538-1549. https://doi.org/10.1074/jbc.M116.760975

APA

Back, C., Sztukowska, M. N., Till, M., Lamont, R. J., Jenkinson, H. F., Nobbs, A., & Race, P. (2017). The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism. Journal of Biological Chemistry, 292(5), 1538-1549. https://doi.org/10.1074/jbc.M116.760975

Vancouver

Back C, Sztukowska MN, Till M, Lamont RJ, Jenkinson HF, Nobbs A et al. The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism. Journal of Biological Chemistry. 2017 Feb 3;292(5):1538-1549. https://doi.org/10.1074/jbc.M116.760975

Author

Back, Catherine ; Sztukowska, Maryta N ; Till, Marisa ; Lamont, Richard J ; Jenkinson, Howard F ; Nobbs, Angela ; Race, Paul. / The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism. In: Journal of Biological Chemistry. 2017 ; Vol. 292, No. 5. pp. 1538-1549.

Bibtex

@article{4e2f6bf4c4114ae999597e373c7fd5dd,
title = "The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism",
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.",
keywords = "Adhesin, intrinsically disordered protein, X-ray crystallography, SAXS, bacterial pathogenesis, microbiology",
author = "Catherine Back and Sztukowska, {Maryta N} and Marisa Till and Lamont, {Richard J} and Jenkinson, {Howard F} and Angela Nobbs and Paul Race",
year = "2017",
month = "2",
day = "3",
doi = "10.1074/jbc.M116.760975",
language = "English",
volume = "292",
pages = "1538--1549",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - The Streptococcus gordonii adhesin CshA protein binds host fibronectin via a catch-clamp mechanism

AU - Back, Catherine

AU - Sztukowska, Maryta N

AU - Till, Marisa

AU - Lamont, Richard J

AU - Jenkinson, Howard F

AU - Nobbs, Angela

AU - Race, Paul

PY - 2017/2/3

Y1 - 2017/2/3

N2 - 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.

AB - 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.

KW - Adhesin

KW - intrinsically disordered protein

KW - X-ray crystallography

KW - SAXS

KW - bacterial pathogenesis

KW - microbiology

UR - http://www.scopus.com/inward/record.url?scp=85011599404&partnerID=8YFLogxK

U2 - 10.1074/jbc.M116.760975

DO - 10.1074/jbc.M116.760975

M3 - Article

VL - 292

SP - 1538

EP - 1549

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -