title: A discrete sequence in a platelet integrin is involved in ligand recognition.
abstract: Platelet membrane glycoprotein IIb-IIIa (gpIIb-IIIa; alpha IIb-beta 3), the most prominent member of the integrin family of adhesion receptors on these cells, mediates platelet aggregation by binding fibrinogen and is critical in thrombosis and haemostasis. A short amino-acid sequence at the carboxy terminus of the gamma chain of fibrinogen is recognized by gpIIb-IIIa and peptides containing this sequence are selectively crosslinked to residues 294-314 of gpIIb. Here we show that an 11-residue peptide from this region of gpIIb inhibits platelet aggregation and binding of fibrinogen to platelets and to purified gpIIb-IIIa, and that it interacts directly with fibrinogen. These results implicate this segment of gpIIb-IIIa in the ligand-binding function of the receptor. Moreover, as this region is highly conserved among integrins, it may have a general function in ligand recognition by this broadly distributed family of adhesion receptors.
authors.affiliation: Committee on Vascular Biology, Research Institute of Scripps Clinic, La Jolla, California 92037.
authors.forename: S E
authors.initials: SE
authors.lastname: D'Souza
authors.forename: M H
authors.initials: MH
authors.lastname: Ginsberg
authors.forename: G R
authors.initials: GR
authors.lastname: Matsueda
authors.forename: E F
authors.initials: EF
authors.lastname: Plow
mesh_terms: D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology; D001665:Binding Sites; D001792:Blood Platelets / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen