5l2d

Publication Abstract from PubMed

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.

The Streptococcus gordonii adhesin CshA binds host fibronectin via a catch-clamp mechanism.,Back CR, Sztukowska MN, Till M, Lamont RJ, Jenkinson HF, Nobbs AH, Race PR J Biol Chem. 2016 Dec 5. pii: jbc.M116.760975. PMID:27920201^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.