Structural determinants within platelet glycoprotein Ib alpha involved in its binding to von Willebrand factor

Platelet adhesion to subendothelial structures upon injury to a vessel wall is one of the first steps in a sequence of reactions critical for the form ation of a haemostatic plug, or in diseased vessels for the development of an arterial thrombus. This adhesion process is mediated by an interaction b etween the glycoprotein (GP) Ib-V-IX complex on the platelet surface with v on Willebrand Factor (vWF), associated with collagen on the subendothelial surface. After this initial adhesion, platelets will activate, resulting in recruitment of additional platelets and adherence to each other to form th e platelet plug or developing thrombus. Several studies to date have attemp ted to identify the regions of the GPIb-V-IX complex that are critical for binding to vWF. The vWF binding site is contained in the 45 kDa N-terminal domain of the GPIb alpha chain. This N-terminal domain is characterized by a structural motif consisting of 7 leucine-rich repeats (LRRs), followed by a double disulphide-bonded loop and an anionic sulphated region. This revi ew summarizes recent research efforts elucidating the characteristics of th e GPIb-vWF interaction. Potential mechanisms that regulate the GPIb-vWF fun ction are discussed, and advances in identifying functional sequences withi n GPIb alpha involved in the binding to vWF are reviewed.