title: The Vibrio cholerae colonization factor GbpA possesses a modular structure that governs binding to different host surfaces.
abstract: Vibrio cholerae is a bacterial pathogen that colonizes the chitinous exoskeleton of zooplankton as well as the human gastrointestinal tract. Colonization of these different niches involves an N-acetylglucosamine binding protein (GbpA) that has been reported to mediate bacterial attachment to both marine chitin and mammalian intestinal mucin through an unknown molecular mechanism. We report structural studies that reveal that GbpA possesses an unusual, elongated, four-domain structure, with domains 1 and 4 showing structural homology to chitin binding domains. A glycan screen revealed that GbpA binds to GlcNAc oligosaccharides. Structure-guided GbpA truncation mutants show that domains 1 and 4 of GbpA interact with chitin in vitro, whereas in vivo complementation studies reveal that domain 1 is also crucial for mucin binding and intestinal colonization. Bacterial binding studies show that domains 2 and 3 bind to the V. cholerae surface. Finally, mouse virulence assays show that only the first three domains of GbpA are required for colonization. These results explain how GbpA provides structural/functional modular interactions between V. cholerae, intestinal epithelium and chitinous exoskeletons.
authors.affiliation: Division of Molecular Microbiology, College of Life Sciences, University of Dundee, Dundee, United Kingdom.
authors.forename: Edmond
authors.initials: E
authors.lastname: Wong
authors.forename: Gustav
authors.initials: G
authors.lastname: Vaaje-Kolstad
authors.forename: Avishek
authors.initials: A
authors.lastname: Ghosh
authors.forename: Ramon
authors.initials: R
authors.lastname: Hurtado-Guerrero
authors.forename: Peter V
authors.initials: PV
authors.lastname: Konarev
authors.forename: Adel F M
authors.initials: AF
authors.lastname: Ibrahim
authors.forename: Dmitri I
authors.initials: DI
authors.lastname: Svergun
authors.forename: Vincent G H
authors.initials: VG
authors.lastname: Eijsink
authors.forename: Nabendu S
authors.initials: NS
authors.lastname: Chatterjee
authors.forename: Daan M F
authors.initials: DM
authors.lastname: van Aalten
mesh_terms: D000818:Animals; D002686:Chitin / Q000737:chemistry / Q000378:metabolism; D018360:Crystallography, X-Ray; D036781:Fimbriae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D054884:Host-Pathogen Interactions / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D008958:Models, Molecular; D030781:Organisms, Genetically Modified; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014734:Vibrio cholerae / Q000235:genetics / Q000254:growth & development / Q000472:pathogenicity / Q000502:physiology
chemical_list: D011956:Receptors, Cell Surface; C022924:colonization factor antigens; D002686:Chitin; D036781:Fimbriae Proteins