Domain shuffling of a highly mutable ligand binding fold drives adhesin generation across the bacterial kingdom

Rob W L Barringer, Alice E Parnell, Aleix Lafita, Vivian Monzon, Catherine Back, Mariusz Madej, Jan Potempa, Angela H Nobbs, Steven G Burston, Alex Bateman, Paul R Race*

*Corresponding author for this work

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


Bacterial fibrillar adhesins are specialised extracellular polypeptides that promote the attachment of bacteria to the surfaces of other cells or materials. Adhesin-mediated interactions are critical for the establishment and persistence of stable bacterial populations within diverse environmental niches and are important determinants of virulence. The fibronectin (Fn) binding fibrillar adhesin CshA, and its paralogue CshB, play important roles in host colonisation by the oral commensal and opportunistic pathogen Streptococcus gordonii. As paralogues are often catalysts for functional diversification, we have probed the early stages of structural and functional divergence in Csh proteins by determining the X-ray crystal structure of the CshB adhesive domain NR2 and characterising its Fn binding properties in vitro. Despite sharing a common fold, CshB_NR2 displays an ~1.7-fold reduction in Fn binding affinity relative to CshA_NR2. This correlates with reduced electrostatic charge in the Fn binding cleft. Complementary bioinformatic studies reveal that homologues of CshA/B_NR2 domains are widely distributed in both Gram-positive and Gram-negative bacteria, where they are found housed within functionally cryptic multi-domain polypeptides. Our findings are consistent with the classification of Csh adhesins and their relatives as members of the recently defined Polymer Adhesin Domain (PAD) family of bacterial proteins.
Original languageEnglish
Pages (from-to)1007-1020
Number of pages14
JournalProteins: Structure, Function, and Bioinformatics
Issue number8
Early online date13 Mar 2023
Publication statusE-pub ahead of print - 13 Mar 2023

Bibliographical note

Funding Information:
This study was funded by BBSRC grants BB/L01386X/1, BB/M012107/1 and BB/T001968/1, and through the award of a BBSRC SWBio Ph.D studentship to RB (BB/T008741/1). AL, AB and VM are supported by European Molecular Biology Laboratory core funds.

Publisher Copyright:
© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.

Structured keywords

  • Bristol BioDesign Institute
  • BrisSynBio


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