Structural Analysis of von Willebrand Factor

The von Willebrand factor (VWF) is a large, multidomain glycoprotein whose modular organization facilitates its diverse physiological functions, primarily in hemostasis. Each domain contributes distinct molecular properties that collectively enable VWF to sense shear force, mediate platelet adhesion, and stabilize coagulation factor VIII (FVIII). In the past decades, structural studies using X-ray crystallography, cryo-electron microscopy (cryo-EM), nuclear magnetic resonance (NMR), and molecular modeling have revealed the architecture of nearly every domain. This review provides an examination of VWF's molecular architecture, the structural basis of its interactions, and the implications of structural insights for disease understanding and therapy.