title: A region of the Yersinia pseudotuberculosis invasin protein that contributes to high affinity binding to integrin receptors.
abstract: The entry of Yersinia pseudotuberculosis into cultured mammalian cells is mediated by the bacterial protein invasin. The mammalian receptors for invasin are five beta1 chain integrins. Site-directed mutagenesis of the aspartate and lysine residues in the 192-amino acid integrin binding domain of invasin was performed to identify regions, in addition to the previously characterized 903-913 region, that are important for integrin binding. One mutation, D811A, resulted in depressed ability of invasin to bind purified alpha5beta1 and to promote bacterial entry. Further mutational analysis of Asp-811 indicated that an oxygen-containing side chain is required at this position. A second nearby residue, Phe-808, was also shown to be important for integrin binding, as an alanine substitution at this site had properties similar to the Asp-811 mutation. This mutational analysis has therefore identified a second region that, in conjunction with residues 903-913, is required for wild type levels of integrin binding. The contribution to binding by two noncontiguous sites in the primary sequence parallels results that indicate two domains of fibronectin are involved in integrin binding.
authors.affiliation: Howard Hughes Medical Institute, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
authors.forename: L H
authors.initials: LH
authors.lastname: Saltman
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: E M
authors.initials: EM
authors.lastname: Zaharias
authors.forename: R R
authors.initials: RR
authors.lastname: Isberg
mesh_terms: D018829:Adhesins, Bacterial; D000595:Amino Acid Sequence; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites; D002478:Cells, Cultured; D004252:DNA Mutational Analysis; D005353:Fibronectins / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D017469:Receptors, Fibronectin / Q000378:metabolism*; D015011:Yersinia pseudotuberculosis / Q000472:pathogenicity / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; D005353:Fibronectins; D017469:Receptors, Fibronectin; C053476:invasin, Yersinia