Structure of the von Willebrand factor domain interacting with glycoprotein Ib

von Willebrand factor is a multifunctional adhesive protein of plasma, platelets, and endothelial cells that mediates a crucial interaction for normal hemostasis and thrombus formation by binding to platelet membrane glycoprotein Ib. We provide here evidence that this function involves two limited noncontiguous regions of the molecule, each contained within 15 amino acid residues, separated in the linear sequence by 205 residues, and maintained in close spatial proximity in the folded molecule by disulfide bonding. Definition of this chemical structure clarifies a fundamental mechanism of platelet adhesion to thrombogenic surfaces and sets the bases for obtaining synthetic replicas that may be used to modulate platelet function.