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Assembling the molecular machinery of coagulation: learning from the adaptive evolution of snake venom proteins.

Dr M.H.A. Bos


Name researcher:

4 years

Amount granted:




Project number:


Project leader:

Dr Mettine H.A. Bos, Dept. Thrombosis and Hemostasis, LUMC
PhD student: Mark Schreuder (Jan. 2015 – Dec. 2018)

About the project

Blood clotting protects humans and animals against injury-induced blood loss. Clotting occurs through a cascade of proteolytic reactions that convert an inactive protease (zymogen) to an active protease. Most of the reactions only occur when the cofactor-protease complexes assemble on a negatively charged phospholipid surface, such as that of activated blood platelets or endothelial cells that line the vessel wall. The overall aim of this project is to unravel the molecular mechanism by which the interaction with phospholipids contributes to these proteolytic activation reactions. To do so, we study blood coagulation proteins that are found in the venom of some Australian snakes. These snakes have adapted these clotting proteins into powerful toxins. One of the induced modifications is that the venom proteins are capable of clotting in solution and as such lack the requirement for membrane binding. In the present study, we aimed to better understand which functional modifications in the snake proteins are coupled to function, in order to explain the lipid-independent function, among others. We have identified a number of structural features in the snake venom proteins that are clearly linked to some unique functions. At this point we are further deciphering the exact mechanism by which these exceptional protein regions exert their function. We anticipate that in the long run when we will have better understanding of these functional regions and sequence, we may be able to identify new targets and contribute to the development of novel therapeutic proteins to treat clotting disorders such as the bleeding disorder hemophilia or, conversely, thrombosis.

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