Structure and function of the von Willebrand factor A1 domain.
The role of von Willebrand factor (VWF) in blocking hemorrhage is centered on its ability to act as a bridging adhesive molecule between platelets and components of the extracellular matrix or other platelets. In the course of chronic vascular diseases, moreover, the same properties of VWF may become the cause of pathological thrombus formation leading to arterial occlusion. There is convincing evidence that VWF functions involving interactions with platelets ultimately depend on binding to the membrane glycoprotein (GP) Ibalpha receptor mediated by the A1 domain. In this review, we present the current knowledge on the structural features of the VWF A1 domain that support its functions.
Roon Research Center for Arteriosclerosis and Thrombosis, Division of Experimental Hemostasis and Thrombosis, Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA. ruggeri@scripps.edu
Kottayil I
KI
Varughese
Reha
R
Celikel
Zaverio M
ZM
Ruggeri
D000595:Amino Acid Sequence; D001665:Binding Sites; D001792:Blood Platelets; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014841:von Willebrand Factor / Q000737:chemistry* / Q000378:metabolism*
D010446:Peptide Fragments; D010975:Platelet Aggregation Inhibitors; D019038:Platelet Glycoprotein GPIb-IX Complex; D014841:von Willebrand Factor