The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture

Catherine Back, Victoria A Higman, Kristian Le Vay, Viren V Patel, Alice E Parnell, Daniel Frankel, Howard F Jenkinson, Steven G Burston, Matthew P Crump, Angela H Nobbs, Paul R Race

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
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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 seventeen ~100-amino-acid-long repeat domains (RDs). 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.
Original languageEnglish
JournalJournal of Biological Chemistry
Early online date30 Mar 2020
Publication statusE-pub ahead of print - 30 Mar 2020

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute


  • adhesin
  • fibril
  • protein folding
  • microbiology
  • bacterial pathogenicity
  • NMR spectroscopy
  • small-angle X-ray scattering (SAXS)
  • virulence factor
  • biofilm
  • CshA
  • synthetic biology


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