The first step in the formation of an arterial thrombus is the interaction of the platelet receptor complex GPIb/V/IX with von Willebrand factor (vWF) bound to exposed collagens. Before platelets can bind to vWF, vWF has to undergo a conformational change that is induced by binding to collagen. We have developed specific antibodies that recognise von Willebrand factor only in its GPIb binding conformation. In the past, we developed models to study platelet-vessel wall interaction under conditions of flow and we have used amongst others site-directed mutagenesis to characterize the important domains within von Willebrand factor, collagen and GPIb involved in these interactions. We have crystallised von Willebrand factor with GPIb to understand this interaction at the atomic level.
Specific aims:
To understand the interaction of vWF with collagen at the atomic level.
To understand the conformational changes at the atomic level that convert vWF into its GPIb binding conformation.
Projectleader: Prof.dr. Ph.G. de Groot