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Lookup NU author(s): Dr Daniel Frankel, Professor Paul RaceORCiD
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© 2020 Back et al.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.
Author(s): Back CR, Higman VA, Le Vay K, Patel VV, Parnell AE, Frankel D, Jenkinson HF, Burston SG, Crump MP, Nobbs AH, Race PR
Publication type: Article
Publication status: Published
Journal: The Journal of Biological Chemistry
Year: 2020
Volume: 295
Issue: 19
Pages: 6689-6699
Print publication date: 08/05/2020
Online publication date: 30/03/2020
Acceptance date: 26/03/2020
ISSN (print): 0021-9258
ISSN (electronic): 1083-315X
Publisher: American Society for Biochemistry and Molecular Biology, Inc.
URL: https://doi.org/10.1074/jbc.RA119.011719
DOI: 10.1074/jbc.RA119.011719
PubMed id: 32229583
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