PLATELET GPIB-V-IX COMPLEX - STRUCTURE, FUNCTION, PHYSIOLOGY, AND PATHOLOGY

In the early phase of primary hemostasis, platelets adhere to damaged vessel wall by binding via the platelet glycoprotein (GP) Ib-V-IX comp lex to von Willebrand factor (vWf) exposed on the subendothelium. The complex is composed of four glycoprotein subunits, GPIb alpha, GPIb be ta, GPIX and GPV, each with a variable number of leucine-rich repeats. GPIb alpha and GPIb beta are linked by a disulphide bridge while GPIX and GPV associate noncovalently with the complex. The study of defect s in the expression of the GPIb-V-IX complex at the platelet surface l eading to pathological disorders, like Bernard-Soulier syndrome (BSS), or in the affinity of platelets for vWf, like pseudo-von Willebrand d isease, has helped to delineate the binding site for vWf on GPIb alpha . However, the mechanism by which the complex binds to vWf has not yet been elucidated but it must involve changes in the conformation of th e molecules as no interaction between platelets and vWf occurs in the plasma. The GPIb-V-IX complex has a binding site for thrombin on GPIb alpha which participates in the platelet activation by that agonist. G PV is also cleaved by thrombin but the function of this proteolysis is not clear. The platelet response to thrombin is slower and weaker whe n the thrombin binding site on GPIb alpha is blocked or cleaved or whe n the GPIb-V-IX complex is not expressed on the platelet surface as in classic BSS, At low doses of thrombin, the rapid activation of the pl atelets via the seven-transmembrane thrombin receptor is dependent on the presence of the GPIb-V-IX complex.