6SZC

NMR structure of repeat domain 13 of the fibrillar adhesin CshA from Streptococcus gordonii.

Summary for 6SZC

• Entry DOI: 10.2210/pdb6szc/pdb
• NMR Information: BMRB: 34439
• Descriptor: Surface-associated protein CshA (1 entity in total)
• Functional Keywords: adhesin, fibril, novel, repeat domain, streptococcus, cell adhesion
• Biological source: Streptococcus gordonii (strain Challis / ATCC 35105 / BCRC 15272 / CH1 / DL1 / V288)
• Total number of polymer chains: 1
• Total formula weight: 12480.74

Authors

Higman, V.A.,Back, C.,Crump, M.P.,Race, P. (deposition date: 2019-10-02, release date: 2020-04-08, Last modification date: 2024-06-19)

Primary citation

Back, C.R.,Higman, V.A.,Le Vay, K.,Patel, V.V.,Parnell, A.E.,Frankel, D.,Jenkinson, H.F.,Burston, S.G.,Crump, M.P.,Nobbs, A.H.,Race, P.R.
The streptococcal multidomain fibrillar adhesin CshA has an elongated polymeric architecture.
J.Biol.Chem., 295:6689-6699, 2020

PubMed Abstract: 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. 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 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.

PubMed: 32229583
DOI: 10.1074/jbc.RA119.011719

Experimental method

SOLUTION NMR