title: Echovirus 1 interaction with the human very late antigen-2 (integrin alpha2beta1) I domain. Identification of two independent virus contact sites distinct from the metal ion-dependent adhesion site.
abstract: The human integrin very late antigen (VLA)-2 (CD49b/CD29) mediates interactions with collagen and is the receptor for echovirus 1. Binding sites for both collagen and echovirus 1 have been mapped to the I domain within the alpha2 subunit of the VLA-2 alpha2beta1 heterodimer. Although murine VLA-2 interacts with collagen, it does not bind virus. We have used isolated human-murine chimeric I domains expressed as glutathione S-transferase fusion proteins in Escherichia coli to identify two groups of amino acids, 199-201 and 212-216, independently involved in virus attachment. These residues are distinct from the metal ion-dependent adhesion site previously demonstrated to be essential for VLA-2 interactions with collagen. Mutations in three metal ion-dependent adhesion site residues that abolish adhesion to collagen had no effect on virus binding. These results confirm that different sites within the I domain are responsible for VLA-2 interaction with extracellular matrix proteins and with viral ligands.
authors.affiliation: Division of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: King
authors.forename: T
authors.initials: T
authors.lastname: Kamata
authors.forename: J A
authors.initials: JA
authors.lastname: Cunningham
authors.forename: J
authors.initials: J
authors.lastname: Emsley
authors.forename: R C
authors.initials: RC
authors.lastname: Liddington
authors.forename: Y
authors.initials: Y
authors.lastname: Takada
authors.forename: J M
authors.initials: JM
authors.lastname: Bergelson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D002352:Carrier Proteins / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D029822:Enterovirus B, Human / Q000378:metabolism*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D016023:Integrins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008670:Metals / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D038981:Receptors, Collagen; D011991:Receptors, Virus / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013045:Species Specificity
chemical_list: D002352:Carrier Proteins; D019012:Integrin beta1; D016023:Integrins; D008670:Metals; D038981:Receptors, Collagen; D011991:Receptors, Virus; D011993:Recombinant Fusion Proteins; D003094:Collagen