First Analysis of a Bacterial Collagen-Binding Protein with Collagen Toolkits: Promiscuous Binding of YadA to Collagens May Explain How YadA Interferes with Host Processes
- 1 July 2010
- journal article
- research article
- Published by American Society for Microbiology in Infection and Immunity
- Vol. 78 (7), 3226-3236
- https://doi.org/10.1128/iai.01057-09
Abstract
The Yersinia adhesin YadA mediates the adhesion of the human enteropathogen Yersinia enterocolitica to collagens and other components of the extracellular matrix. Though YadA has been proposed to bind to a specific site in collagens, the exact binding determinants for YadA in native collagen have not previously been elucidated. We investigated the binding of YadA to collagen Toolkits, which are libraries of triple-helical peptides spanning the sequences of type II and III human collagens. YadA bound to many of them, in particular to peptides rich in hydroxyproline but with few charged residues. We were able to block the binding of YadA to collagen type IV with the triple-helical peptide (Pro-Hyp-Gly)10, suggesting that the same site in YadA binds to triple-helical regions in network-forming collagens as well. We showed that a single Gly-Pro-Hyp triplet in a triple-helical peptide was sufficient to support YadA binding, but more than six triplets were required to form a tight YadA binding site. This is significantly longer than the case for eukaryotic collagen-binding proteins. YadA-expressing bacteria bound promiscuously to Toolkit peptides. Promiscuous binding could be advantageous for pathogenicity in Y. enterocolitica and, indeed, for other pathogenic bacteria. Many of the tightly binding peptides are also targets for eukaryotic collagen-binding proteins, and YadA was able to inhibit the interaction between selected Toolkit peptides and platelets. This leads to the intriguing possibility that YadA may interfere in vivo with host processes mediated by endogenous collagen-binding proteins.Keywords
This publication has 79 references indexed in Scilit:
- Synergism between platelet collagen receptors defined using receptor-specific collagen-mimetic peptide substrata in flowing bloodBlood, 2010
- Platelets Amplify Inflammation in Arthritis via Collagen-Dependent Microparticle ProductionScience, 2010
- Structural Insights into the Interactions between Platelet Receptors and Fibrillar CollagenJournal of Biological Chemistry, 2009
- Functional Mapping of YadA- and Ail-Mediated Binding of Human Factor H toYersinia enterocoliticaSerotype O:3Infection and Immunity, 2008
- Characterization of Complement Factor H Binding toYersinia enterocoliticaSerotype O:3Infection and Immunity, 2008
- Unusual, Virulence Plasmid-Dependent Growth Behavior of Yersinia enterocolitica in Three-Dimensional Collagen GelsJournal of Bacteriology, 2008
- EmaA, a Potential Virulence Determinant of Aggregatibacter actinomycetemcomitans in Infective EndocarditisInfection and Immunity, 2008
- Identification of a major GpVI-binding locus in human type III collagenBlood, 2008
- The Yersinia adhesin YadA binds to a collagenous triple-helical conformation but without sequence specificityProtein Engineering, Design and Selection, 2008
- yadBC of Yersinia pestis , a New Virulence Determinant for Bubonic PlagueInfection and Immunity, 2008