I have a love-hate affair with BBC Science News. On the one hand there is a huge variety of articles on all sorts of interesting things. Then now and again something chemistry / biochemistry based will turn up and I want to read about it in-depth, but they never give a paper reference!
Now it’s even worse because I don’t have journal access – so even when I find the paper I can’t view it!
Anyway the BBC News article is here and the paper is here, abstract:
Mechanoenzymatic Cleavage of the Ultralarge Vascular Protein von Willebrand Factor
Xiaohui Zhang, Kenneth Halvorsen, Cheng-Zhong Zhang, Wesley P. Wong, Timothy A. Springer
Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that elongational forces in the range experienced by VWF in the vasculature unfold the A2 domain, and only the unfolded A2 domain is cleaved by ADAMTS13. In shear flow, tensile force on a VWF multimer increases with the square of multimer length and is highest at the middle, providing an efficient mechanism for homeostatic regulation of VWF size distribution by force-induced A2 unfolding and cleavage by ADAMTS13, as well as providing a counterbalance for VWF-mediated platelet aggregation.
So basically, the flow of blood pushes the multimeric VWF protein into an open conformation where the protease can get to the cleavage site. The bigger the VWF protein and the greater the blood pressure at that particular point, the more the protein structure unfolds and the easier it is for cleavage to occur, regulating the size of the VWF protein.
I find blood clotting an interesting topic as I have Von Willebrand’s Syndrome, although I can’t remember what type and it doesn’t rear its head very often. I’m currently prescribed tranexamic acid for when I’ve been bleeding – it’s more usually given for heavy periods so I sometimes get asked questions at new GPs and the pharmacist!
