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; K-d = 2 +/- 0.8 x 10(-5) M). This interaction is Ca2+-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 mu M). 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.