THE VON-WILLEBRAND-FACTOR A3 DOMAIN DOES NOT CONTAIN A METAL ION-DEPENDENT ADHESION SITE MOTIF

von Willebrand factor (vWF) is a multimeric plasma protein that mediat es platelet adhesion to exposed subendothelium at sites of vascular in jury, The A3 domain of vWF (vWF-A3) forms the principal binding site f or collagens type I and III, We report here the crystal structure of t he vWF A3 domain at 2.2-Angstrom resolution, As expected, the structur e is similar to the integrin I domain but with several novel features, Sequence alignments had suggested that the domain contained an integr in metal ion-dependent adhesion site (MIDAS) motif, but the crystal st ructure shows that the motif is modified and that no metal ion is boun d, We have introduced mutations into the vestigial MIDAS motif and rep ort that, unlike the I domain of integrin (alpha 2 beta 1, vWF-A3 cont inues to bind collagen after disruption of the motif. We conclude that collagen recognition by vWF-A3 occurs by a mechanism different from t hat of the integrin alpha 2 beta 1.