Toggle Main Menu Toggle Search

Open Access padlockePrints

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

Lookup NU author(s): Professor Paul RaceORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC. Bacterial fibrillar adhesins are specialized 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 colonization 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 characterizing 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.

Publication metadata

Author(s): Barringer R, Parnell AE, Lafita A, Monzon V, Back CR, Madej M, Potempa J, Nobbs AH, Burston SG, Bateman A, Race PR

Publication type: Article

Publication status: Published

Journal: Proteins: Structure, Function and Bioinformatics

Year: 2023

Volume: 91

Issue: 8

Pages: 1007-1020

Print publication date: 01/08/2023

Online publication date: 13/03/2023

Acceptance date: 28/02/2023

Date deposited: 20/12/2023

ISSN (print): 0887-3585

ISSN (electronic): 1097-0134

Publisher: John Wiley and Sons Inc.


DOI: 10.1002/prot.26487

PubMed id: 36912614


Altmetrics provided by Altmetric


Funder referenceFunder name
European Molecular Biology Laboratory core funds