A discrete sequence in a platelet integrin is involved in ligand recognition

Nature. 1991 Mar 7;350(6313):66-8. doi: 10.1038/350066a0.

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.

MeSH terms

  • Amino Acid Sequence
  • Antibodies / pharmacology
  • Binding Sites
  • Blood Platelets / metabolism
  • Fibrinogen / metabolism
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Membrane Glycoproteins / chemistry
  • Platelet Membrane Glycoproteins / metabolism
  • Platelet Membrane Glycoproteins / pharmacology*

Substances

  • Antibodies
  • Peptide Fragments
  • Platelet Aggregation Inhibitors
  • Platelet Membrane Glycoproteins
  • Fibrinogen