title: Structural basis for Myf and Psa fimbriae-mediated tropism of pathogenic strains of Yersinia for host tissues.
abstract: Three pathogenic species of the genus Yersinia assemble adhesive fimbriae via the FGL-chaperone/usher pathway. Closely related Y. pestis and Y. pseudotuberculosis elaborate the pH6 antigen (Psa), which mediates bacterial attachment to alveolar cells of the lung. Y. enterocolitica, instead, assembles the homologous fimbriae Myf of unknown function. Here, we discovered that Myf, like Psa, specifically recognizes β1-3- or β1-4-linked galactose in glycosphingolipids, but completely lacks affinity for phosphatidylcholine, the main receptor for Psa in alveolar cells. The crystal structure of a subunit of Psa (PsaA) complexed with choline together with mutagenesis experiments revealed that PsaA has four phosphatidylcholine binding pockets that enable super-high-avidity binding of Psa-fibres to cell membranes. The pockets are arranged as six tyrosine residues, which are all missing in the MyfA subunit of Myf. Conversely, the crystal structure of the MyfA-galactose complex revealed that the galactose-binding site is more extended in MyfA, enabling tighter binding to lactosyl moieties. Our results suggest that during evolution, Psa has acquired a tyrosine-rich surface that enables it to bind to phosphatidylcholine and mediate adhesion of Y. pestis/pseudotuberculosis to alveolar cells, whereas Myf has specialized as a carbohydrate-binding adhesin, facilitating the attachment of Y. enterocolitica to intestinal cells.
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.
authors: Natalia
authors: N
authors: Pakharukova
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.|Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, Uppsala BioCentre, P.O. BOX 7016, Uppsala, 75007, Sweden.
authors: Saumendra
authors: S
authors: Roy
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.
authors: Minna
authors: M
authors: Tuittila
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.
authors: Mohammad M
authors: MM
authors: Rahman
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.
authors: Sari
authors: S
authors: Paavilainen
authors: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, P.O. BOX 440, Göteborg, 40530, Sweden.
authors: Anna-Karin
authors: AK
authors: Ingars
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.|Department of Biochemistry/Biotechnology, University of Turku, Tykistökatu 6A, Turku, 20014, Finland.
authors: Maksym
authors: M
authors: Skaldin
authors: Department of Biochemistry/Biotechnology, University of Turku, Tykistökatu 6A, Turku, 20014, Finland.
authors: Urpo
authors: U
authors: Lamminmäki
authors: Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, Uppsala BioCentre, P.O. BOX 7016, Uppsala, 75007, Sweden.
authors: Torleif
authors: T
authors: Härd
authors: Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, The Sahlgrenska Academy, University of Gothenburg, P.O. BOX 440, Göteborg, 40530, Sweden.
authors: Susann
authors: S
authors: Teneberg
authors: Department of Chemistry, University of Turku, Turku, Joint Biotechnology Laboratory, Arcanum, Vatselankatu 2, Turku, 20500, Finland.|Department of Chemistry and Biotechnology, Swedish University of Agricultural Sciences, Uppsala BioCentre, P.O. BOX 7016, Uppsala, 75007, Sweden.
authors: Anton V
authors: AV
authors: Zavialov
mesh_terms: D018829:Adhesins, Bacterial / Q000378:metabolism; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D001665:Binding Sites; D036781:Fimbriae Proteins / Q000378:metabolism; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D018523:Tropism / Q000235:genetics; D014774:Virulence / Q000235:genetics; D015007:Yersinia / Q000378:metabolism*; D015008:Yersinia enterocolitica / Q000378:metabolism; D015010:Yersinia pestis / Q000378:metabolism; D015011:Yersinia pseudotuberculosis / Q000378:metabolism
chemical_list: D018829:Adhesins, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018832:Molecular Chaperones; C093279:MyfA protein, Yersinia; D036781:Fimbriae Proteins