Von Willebrand factor (vWF) binding to platelets under high fluid shear is an important step regulating atherothrombosis. We applied light and small-angle neutron scattering to study the solution structure of human vWF multimers and protomer. Results suggest that these proteins resemble prolate ellipsoids with radius of gyration (Rg) of ~75nm and ~30nm for multimer and protomer respectively. The ellipsoid dimensions/radii are 175×28nm for multimers and 70×9.1nm for protomers. Substructural repeat domains are evident within multimeric-vWF that are indicative of elements of the protomer quarternary structure (16nm) and individual functional domains (4.5nm). Amino acids occupy only ~2% volume of multimer and protomer ellipsoids, compared to other proteins like albumin (98%) and fibrinogen (35%). vWF treatment with Guanidine?HCl, which increases vWF susceptibility to proteolysis by ADAMTS-13, causes local structural changes at length scales
Revised: October 26, 2007 |
Published: December 15, 2006
Citation
Singh I., H. Shankaran, M.E. Beauharnois, Z. Xiao, P. Alexandridis, and S. Neelamegham. 2006.Solution structure of human von Willebrand factor studied using small angle nuetron scattering.Journal of Biological Chemistry 281, no. 50:38266-38275.PNNL-SA-49749.