Abstract
EMBO J 30 19, 4098–4111 (2011); published online August 19 2011 The large glycoprotein von Willebrand factor (vWF) serves an important role in orchestrating the blood vessel's response to injury. It is released from activated endothelial cells and forms long multimeric strings that bind exposed extracellular matrix and circulating platelets and thereby initiate the formation of a platelet plug sealing the wound. Central to this process is the rapid transition of multimeric vWF from a tightly packed storage form present in acidic intraendothelial granules, to the elongated string that is active at neutral vascular pH. In this issue of The EMBO Journal, Zhou and coworkers now provide compelling structural evidence for internal conformational changes that accompany this transition and thereby serve important regulatory functions. They show that the C-terminal part of the protein zips up into a dimeric bouquet at the acidic internal pH of the storage granules but opens up at the neutral pH of plasma, thereby assisting the establishment of elongated vWF strings capable of efficiently capturing platelets.