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.
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)
The Heidelberg Institute for Theoretical Studies (HITS) was established in 2010 by the physicist and SAP co-founder Klaus Tschira (1940-2015) and the Klaus Tschira Foundation as a private, non-profit research institute. HITS conducts basic research in the natural sciences, mathematics and computer science, with a focus on the processing, structuring, and analyzing of large amounts of complex data and the development of computational methods and software. The research fields range from molecular biology to astrophysics. The shareholders of HITS are the HITS-Stiftung, which is a subsidiary of the Klaus Tschira Foundation, Heidelberg University and the Karlsruhe Institute of Technology (KIT). HITS also cooperates with other universities and research institutes and with industrial partners. The base funding of HITS is provided by the HITS Stiftung with funds received from the Klaus Tschira Foundation. The primary external funding agencies are the Federal Ministry of Education and Research (BMBF), the German Research Foundation (DFG), and the European Union.