The organizing principle of the platelet glycoprotein Ib-IX-V complex.

The glycoprotein (GP)Ib-IX-V complex is the platelet receptor for von Willebrand factor and many other molecules that are critically involved in hemostasis and thrombosis. The lack of functional GPIb-IX-V complexes on the platelet surface is the cause of Bernard-Soulier syndrome, a rare hereditary bleeding disorder that is also associated with macrothrombocytopenia. GPIb-IX-V contains GPIbα, GPIbβ, GPIX and GPV subunits, all of which are type I transmembrane proteins containing leucine-rich repeat domains. Although all of the subunits were identified decades ago, not until recently did the mechanism of complex assembly begin to emerge from a systematic characterization of inter-subunit interactions. This review summarizes the forces driving the assembly of GPIb-IX-V, discusses their implications for the pathogenesis of Bernard-Soulier syndrome, and identifies questions that remain about the structure and organization of GPIb-IX-V.