[The glycoprotein IIb/IIIa complex of the platelets. An activation-dependent integrin]

The glycoprotein (GP) IIb/IIIa complex is the most abundant platelet membrane receptor (approximately 80,000 copies/platelet). The GP IIb/IIIa complex is an adhesion receptor belonging to the integrin superfamily; it can bind five adhesive proteins containing the arginine-glycine-aspartic acid (RGD) sequence in their structure: fibrinogen (Fg), von Willebrand factor (vWf), thrombospondin (Tsp), fibronectin (Fn) and vitronectin (Vn). Fg mediates platelet aggregation; vWf, Tsp and Fn are large molecules that support platelet adhesion to vessel wall; Vn is a molecular connection among hemostasis and others physiological processes. The complex is presents at any time on the platelet surface, but macromolecular ligands cannot access to their receptor because of steric hindrances intrinsic to the complex itself or its microenvironment. Adhesive proteins can bind to the complex only after platelets become activated; following platelet stimulation and ligand binding a conformational change takes place, accompanied by expression of new epitopes termed LIBS (ligand-induced binding sites). The complex-bound fibrinogen undergoes to a progressive rearrangement which increases the adhesive function of the molecule. The RGD sequence present in adhesive proteins, in addition to its receptor role, may serve as a trigger sequence that induces a high affinity ligand-binding state in the GP IIb/IIIa complex. The different domains of adhesive proteins can bind to platelet surface receptors, other than GP IIb/IIIa, so realizing multiple ligand-receptor interactions.