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 × 10−5 M). This interaction is Ca2+-independent and can be partially inhibited with synthetic fibrinogen γ-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 = 170μM). 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.
