Structural mix-n-match reveals molecular secrets of platelets.

Bostjan Kobe THE UNIVERSITY OF QUEENSLAND Understanding the mechanism of platelet activation requires the knowledge of the structural organization of the glycoprotein (GP) Ib-IX-V receptor. In this issue of Blood, an innovative structural approach was used to shed light on the interaction between GPIb and GPIX subunits.1 The GPIb-IX-V complex serves as the platelet receptor that mediates binding to collagen-bound von Willebrand factor (VWF) at sites of vascular injury, leading to platelet activation and thrombus formation.2 GPIbIX-V also binds many other ligands, the functional consequences of which are more obscure; in the case of thrombin even despite the availability of structural information.3 The process of platelet activation must be tightly regulated because dysregulated thrombus formation blocks blood vessels and leads to ischemia, for example, in heart attack and ischemic stroke. Defects in GPIb-IX-V lead to the bleeding disorder Bernard-Soulier syndrome. Three-dimensional structural information of components of signaling pathways and their interactions is essential for an in-depth understanding of processes such as platelet