Crystal structure of the von Willebrand Factor A1 domain and implications for the binding of platelet glycoprotein Ib.
Abstract
von Willebrand Factor (vWF) is a multimeric protein that mediates platelet adhesion to exposed subendothelium at sites of vascular injury under conditions of high flow/shear. The A1 domain of vWF (vWF-A1) forms the principal binding site for platelet glycoprotein Ib (GpIb), an interaction that is tightly regulated. We report here the crystal structure of the vWF-A1 domain at 2.3-A resolution. As expected, the overall fold is similar to that of the vWF-A3 and integrin I domains. However, the structure also contains N- and C-terminal arms that wrap across the lower surface of the domain. Unlike the integrin I domains, vWF-A1 does not contain a metal ion-dependent adhesion site motif. Analysis of the available mutagenesis data suggests that the activator botrocetin binds to the right-hand face of the domain containing helices alpha5 and alpha6. Possible binding sites for GpIb are the front and upper surfaces of the domain. Natural mutations that lead to constitutive GpIb binding (von Willebrand type IIb disease) cluster in a different site, at the interface between the lower surface and the terminal arms, suggesting that they disrupt a regulatory region rather than forming part of the primary GpIb binding site. A possible pathway ...Continue Reading
References
Crystal structure of the A3 domain of human von Willebrand factor: implications for collagen binding
Citations
Related Concepts
Related Feeds
Adhesion Molecules in Health and Disease
Cell adhesion molecules are a subset of cell adhesion proteins located on the cell surface involved in binding with other cells or with the extracellular matrix in the process called cell adhesion. In essence, cell adhesion molecules help cells stick to each other and to their surroundings. Cell adhesion is a crucial component in maintaining tissue structure and function. Discover the latest research on adhesion molecule and their role in health and disease here.
ASBMB Publications
The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.
Blood Clotting Disorders
Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.