Article Metrics


Online attention

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

DOI: 10.1074/jbc.M116.760975 DOI Help

Authors: Catherine R. Back (University of Bristol) , Maryta N. Sztukowska (University of Louisville) , Marisa Till (University of Bristol) , Richard J. Lamont (University of Louisville) , Howard F. Jenkinson (University of Bristol) , Angela H. Nobbs (University of Bristol) , Paul R. Race (University of Bristol)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Biological Chemistry

State: Published (Approved)
Published: December 2016

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. Due to their size and often elaborate multi-domain 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 colonisation by Streptococcus gordonii, an oral commensal and opportunistic pathogen of animals and humans. CshA binds the high-molecular-weight 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 are 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, SAXS, and complementary biophysical methods. In vitro binding studies support a hitherto 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 neighbouring 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 towards the development of anti-adhesive agents that target S. gordonii and related streptococci.

Journal Keywords: adhesin; bacterial pathogenesis; intrinsically disordered protein; microbiology; small-angle X-ray scattering (SAXS); X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I22-Small angle scattering & Diffraction

Discipline Tags:

Technical Tags: