von Willebrand factor

Force-triggered blood coagulation

30 11 2014

Blood coagulation is a complex phenomenon requiring the activation of a series of proteins upon changes in the physiological flow of blood inside blood vessels. The von Willebrand Factor is majorly involved in blood coagulation by a mechanism that is only partially known. Force acting on the protein upon changes in blood shear flow cause a partial unfolding of the structure leading to the exposure of protein binding sites, implying activation, as well as a cleavage site recognized by the ADAMTS13 protein, resulting in deactivation. By means of Molecular Dynamics simulations interfaced to experimental techniques within the DFG funded research group SHENC, we aim at a molecular understanding of the mechanism underlying force-regulated vWF function and related bleeding and thrombosis diseases.
The picture shows the dimeric structure of the cysteine rich knot at the very C-terminus of vWF. By using Molecular Dynamics simulations, we recently found evidence for that disease mutations in this region abolish disulfide bonds and/or lead to altered dynamics hampering the recognition by protein disulfide isomerase, with severe consequences for vWF maturation. More more details, see our joint publication with Maria Brehm and coworkers [1].

[1] Brehm et al. von Willebrand disease type 2A phenotypes IIC, IID and IIE: A day in the life of shear-stressed mutant von Willebrand factor. Thromb Haemost. 112: 96-108 (2014)​

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