Glycoprotein IIb peptide 656-667 mimics the fibrinogen gamma chain 402-411 binding site on platelet integrin GPIIb/IIIa.
The human integrin glycoprotein IIb/IIIa complex plays a central role in haemostasis as an inducible receptor for fibrinogen and other adhesive proteins at the platelet plasma membrane. Current evidence indicates that the ligand-binding domain of GPIIb/IIIa is discontinuous and placed at the subunit interface. Here we show that a synthetic peptide containing the polypeptide stretch GPIIb 656-667, which is hidden within the resting platelet GPIIb/IIIa heterodimer but becomes exposed following platelet activation with thrombin, binds to soluble fibrinogen (n = 2.3 +/- 1.3; Kd = 2 +/- 0.8 x 10(-5) M). This interaction is Ca(2+)-independent and can be partially inhibited with synthetic fibrinogen gamma-chain peptide 400-411 but not with GRGDS. In addition, peptide GPIIb 656-667 inhibits in a dose-dependent manner the aggregation of activated platelets (IC50 = 170 microM). Altogether, our results indicate that the GPIIb 656-667 region may form part of the inducible fibrinogen binding site and may not overlap with the integrin RGD-recognition domain.
Calvete
J J
JJ
Instituto de Química-Física, Rocasolano CSIC, Madrid, Spain.
Rivas
G
G
Schäfer
W
W
McLane
M A
MA
Niewiarowski
S
S
D000595:Amino Acid Sequence; D001665:Binding Sites; D002118:Calcium / Q000494:pharmacology; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D015539:Platelet Activation; D010974:Platelet Aggregation / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D013917:Thrombin / Q000494:pharmacology
D009842:Oligopeptides; D010446:Peptide Fragments; D010980:Platelet Membrane Glycoproteins; C047981:arginyl-glycyl-aspartic acid; D005340:Fibrinogen; D013917:Thrombin; D002118:Calcium