title: Evidence for novel binding sites on the platelet glycoprotein IIb and IIIa subunits and immobilized fibrinogen.
abstract: The present study was designed to examine the interaction of the purified platelet glycoprotein IIb-IIIa complex (GP IIb-IIIa or integrin alpha IIb beta 3) and the individual subunits of the complex with immobilized fibrinogen. Although 125I-GP IIb-IIIa binding to fibrinogen immobilized on Sepharose was specific, this interaction exhibited properties distinct from those of reversible fibrinogen binding to platelets: 125I-GP IIb-IIIa binding appeared irreversible, but non-covalent, Ca(2+)-independent, and was inhibited only weakly, or not at all, by the anti-(GP IIb-IIIa) monoclonal antibodies 10E5 and 7E3 and synthetic peptides from known platelet-binding domains of fibrinogen. Reversibly dissociated GP IIb or GP IIIa subunits inhibited 125I-GP IIb-IIIa binding to immobilized fibrinogen and bound directly to the fibrinogen. However, these subunits did not bind to peptides derived from known platelet-binding domains within the fibrinogen alpha- and gamma-chains, although the GP IIb-IIIa complex did. These results show that the complexed form of full-length GP IIb and GP IIIa is required for binding to these synthetic peptides, but not necessarily for binding to immobilized fibrinogen. Thus GP IIb-IIIa can bind to immobilized fibrinogen by a distinct mechanism that appears to involve novel binding sites on each subunit of the GP IIb-IIIa complex and on fibrinogen.
authors.affiliation: Gladstone Institute of Cardiovascular Disease, University of California, San Francisco 94141-9100.
authors.forename: L V
authors.initials: LV
authors.lastname: Parise
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: L
authors.initials: L
authors.lastname: Nannizzi
authors.forename: A B
authors.initials: AB
authors.lastname: Criss
authors.forename: D R
authors.initials: DR
authors.lastname: Phillips
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005340:Fibrinogen / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D012685:Sepharose
chemical_list: D046911:Macromolecular Substances; D010980:Platelet Membrane Glycoproteins; D005340:Fibrinogen; D012685:Sepharose