title: A beta 3 integrin mutation abolishes ligand binding and alters divalent cation-dependent conformation.
abstract: The ligand-binding function of integrin adhesion receptors depends on divalent cations. A mutant alpha IIb beta 3 integrin (platelet gpIIb/IIIa) that lacks ligand recognition shows immunologic evidence of a perturbed interaction with divalent cations. This was found to be caused by a G----T mutation that resulted in an Asp119----Tyr119 substitution in the beta 3 subunit. This residue is proximal to bound ligand and is in a conserved region among integrins that are enriched in oxygenated residues. The spacing of these residues aligns with the calcium-binding residues in EF hand proteins, suggesting interaction with receptor-bound divalent cation as a mechanism of ligand binding common to all integrins.
authors.affiliation: Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, CA 92037.
authors.forename: J C
authors.initials: JC
authors.lastname: Loftus
authors.forename: T E
authors.initials: TE
authors.lastname: O'Toole
authors.forename: E F
authors.initials: EF
authors.lastname: Plow
authors.forename: A
authors.initials: A
authors.lastname: Glass
authors.forename: A L
authors.initials: AL
authors.lastname: Frelinger
authors.forename: M H
authors.initials: MH
authors.lastname: Ginsberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001224:Aspartic Acid; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D016023:Integrins / Q000235:genetics* / Q000378:metabolism; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D010980:Platelet Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011487:Protein Conformation; D012689:Sequence Homology, Nucleic Acid; D014443:Tyrosine
chemical_list: D016023:Integrins; D008024:Ligands; D046911:Macromolecular Substances; D015345:Oligonucleotide Probes; D010980:Platelet Membrane Glycoproteins; D001224:Aspartic Acid; D014443:Tyrosine