Mechanoenzymatic Cleavage of the Ultralarge Vascular Protein von Willebrand Factor
- 5 June 2009
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 324 (5932), 1330-1334
- https://doi.org/10.1126/science.1170905
Abstract
Dissecting VWF's Thrombogenic Potential: Von Willebrand factor (VWF) is secreted from cells in an ultralarge form (ULVWF) in response to thrombogenic stimuli. Shear forces expose a binding site for platelets, enabling formation of a hemostatic plug. The thrombogenic potential of VWF correlates with its length and is regulated by proteolytic cleavage of the A2 domain. Zhang et al. (p. 1330 ; see the Perspective by Gebhardt and Rief ) now combine single molecule data and polymer dynamics theory to show that shear forces in the circulation are sufficient to unfold the A2 domain and allow cleavage of multimers with more than about 200 monomers. The A2 domain may thus represent the “shear bolt” of VWF, unfolding when multimers experience high forces to allow cleavage and down-regulation of thrombogenic potential.Keywords
This publication has 33 references indexed in Scilit:
- Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificityBlood, 2008
- Platelet-VWF complexes are preferred substrates of ADAMTS13 under fluid shear stressBlood, 2008
- High-Resolution, Single-Molecule Measurements of Biomolecular MotionAnnual Review of Biophysics and Biophysical Chemistry, 2007
- Shear-induced unfolding triggers adhesion of von Willebrand factor fibersProceedings of the National Academy of Sciences of the United States of America, 2007
- Force-Induced Prolyl Cis−Trans Isomerization in Elastin-like PolypeptidesJournal of the American Chemical Society, 2007
- Exosite interactions contribute to tension-induced cleavage of von Willebrand factor by the antithrombotic ADAMTS13 metalloproteaseProceedings of the National Academy of Sciences of the United States of America, 2006
- Shear-Flow-Induced Unfolding of Polymeric GlobulesPhysical Review Letters, 2006
- Entropic Elasticity of λ-Phage DNAScience, 1994
- Reaction-rate theory: fifty years after KramersReviews of Modern Physics, 1990
- Flow-induced scission of isolated macromoleculesThe Journal of Chemical Physics, 1988