A DISCRETE SEQUENCE IN A PLATELET INTEGRIN IS INVOLVED IN LIGAND RECOGNITION

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 1-5. A short amino-acid sequence at the carboxy terminus of the gamma-chain of fibrinogen is recognized by gpIIb-IIIa (ref. 6) and peptides containing this sequence are selectively crosslinked to residues 294-314 of gpIIb (ref. 7). 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.