The I domain is essential for echovirus 1 interaction with VLA-2.
VLA-2, the alpha 2 beta 1 integrin, mediates cell adhesion to collagen and laminin, and is the receptor for the human pathogen echovirus 1. Because of its similarity to domains present in other proteins that interact with collagen, a 191 amino acid region within the alpha 2 subunit (the I domain) has been proposed as a potential site for ligand interactions. Although the alpha 2 subunits of human and murine VLA-2 are 84% identical, human alpha 2 promotes virus binding whereas murine alpha 2 does not. We used murine/human chimeric alpha 2 molecules to identify regions of the human molecule essential for virus binding. Virus bound efficiently to a chimeric protein in which the human I domain was inserted into murine alpha 2, indicating that the human I domain is responsible for specific virus interactions. Monoclonal antibodies that inhibited virus attachment all recognized epitopes within the human I domain, further suggesting that virus interacts with this portion of the molecule. Similarly, antibodies that prevented VLA-2-mediated cell adhesion to collagen also mapped to the I domain. These results indicate that the I domain plays a role in VLA-2 interactions both with virus and with extracellular matrix ligands.
Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115.
J M
JM
Bergelson
N F
NF
St John
S
S
Kawaguchi
R
R
Pasqualini
F
F
Berdichevsky
M E
ME
Hemler
R W
RW
Finberg
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016466:CHO Cells; D002417:Cattle; D002448:Cell Adhesion; D003094:Collagen; D006224:Cricetinae; D029822:Enterovirus B, Human / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D016029:Receptors, Very Late Antigen / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D016029:Receptors, Very Late Antigen; D011993:Recombinant Fusion Proteins; D003094:Collagen