Cut it, but not so fast!

Blood clotting is an amazing biological process in which injured blood vessels are plugged by platelets –flowing in our blood stream– to stop bleeding. Platelets however need of a “molecular tape” to adhere at the site of injury. Once the plug has been formed, and the injured site is closed, a molecular scissor cuts the tape, to prevent the endless growth of the plug that could dangerously block the entire vessel. The tape is a protein called von Willebrand factor (or simply VWF) and the scissor a protease named ADAMTS13. In a multidisciplinary study, combining atomistic simulations and experiments, we clarify how a small alteration in the molecular tape (VWF) can lead to a dramatic acceleration of the cutting process by ADAMTS13, thereby resulting in unwanted bleeding. This information proves valuable for the development of highly sensitive tools that can be used in clinical diagnosis.

Related publication:

C Aponte-Santamaría, S Lippok, J Mittag, T Obser, R Schneppenheim, C Baldauf, F Gräter, U Buddee, and JO Rädler. Mutation G1629E increases von Willebrand factor cleavage via a cooperative destabilization mechanism. Biophys. J. 112: 57-65.10 January 2017 (link)