von Willebrand factor conformation and adhesive function is modulated by an internalized water molecule.
Platelet participation in hemostasis and arterial thrombosis requires the binding of glycoprotein (GP) Ibalpha to von Willebrand factor (vWF). Hemodynamic forces enhance this interaction, an effect mimicked by the substitution I546V in the vWF A1 domain. A water molecule becomes internalized near the deleted Ile methyl group. The change in hydrophobicity of the local environment causes positional changes propagated over a distance of 27 A. As a consequence, a major reorientation of a peptide plane occurs in a surface loop involved in GP Ibalpha binding. This distinct vWF conformation shows increased platelet adhesion and provides a structural model for the initial regulation of thrombus formation.
Celikel
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R
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
Z M
ZM
Varughese
K I
KI
D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology*; D006439:Hemodynamics; D008958:Models, Molecular; D011485:Protein Binding; D011487:Protein Conformation; D014867:Water / Q000737:chemistry; D014841:von Willebrand Factor / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology
D014841:von Willebrand Factor; D014867:Water