Browse by author
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.
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.
URL: https://doi.org/10.1002/prot.26487
DOI: 10.1002/prot.26487
Data Access Statement: The X-ray crystal structure of CshB_NR2 has been deposited in the PDB with the accession code 6YZG. The data that support the findings of this study are available as supplementary files.
PubMed id: 36912614
Altmetrics provided by Altmetric
