The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture.

Autor:	Back CR; Bristol Dental School, University of Bristol, Bristol BS1 2LY, United Kingdom.; School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.; BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom., Higman VA; School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom., Le Vay K; School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.; Bristol Centre for Functional Nanomaterials, H. H. Wills Physics Laboratory, University of Bristol, Bristol BS8 1TL, United Kingdom., Patel VV; School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom., Parnell AE; School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.; BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom., Frankel D; School of Engineering, Newcastle University, Newcastle-upon-Tyne NE1 7RU, United Kingdom., Jenkinson HF; Bristol Dental School, University of Bristol, Bristol BS1 2LY, United Kingdom., Burston SG; School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.; BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom., Crump MP; BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom.; School of Chemistry, University of Bristol, Bristol BS8 1TS, United Kingdom., Nobbs AH; Bristol Dental School, University of Bristol, Bristol BS1 2LY, United Kingdom Angela.Nobbs@bristol.ac.uk., Race PR; School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom Paul.Race@bristol.ac.uk.; BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2020 May 08; Vol. 295 (19), pp. 6689-6699. Date of Electronic Publication: 2020 Mar 30.
DOI:	10.1074/jbc.RA119.011719
Abstrakt:	The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. Streptococcus gordonii is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans. The fibrillar adhesin CshA is an important determinant of S. gordonii adherence, forming peritrichous fibrils on its surface that bind host cells and other microorganisms. CshA possesses a distinctive multidomain architecture comprising an N-terminal target-binding region fused to 17 repeat domains (RDs) that are each ∼100 amino acids long. Here, using structural and biophysical methods, we demonstrate that the intact CshA repeat region (CshA_RD1-17, domains 1-17) forms an extended polymeric monomer in solution. We recombinantly produced a subset of CshA RDs and found that they differ in stability and unfolding behavior. The NMR structure of CshA_RD13 revealed a hitherto unreported all β-fold, flanked by disordered interdomain linkers. These findings, in tandem with complementary hydrodynamic studies of CshA_RD1-17, indicate that this polypeptide possesses a highly unusual dynamic transitory structure characterized by alternating regions of order and disorder. This architecture provides flexibility for the adhesive tip of the CshA fibril to maintain bacterial attachment that withstands shear forces within the human host. It may also help mitigate deleterious folding events between neighboring RDs that share significant structural identity without compromising mechanical stability. (© 2020 Back et al.)
Databáze:	MEDLINE
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