Deciphering the shape and structure of ADAMTS13 - for highly specific clotting control

The structural basis of ADAMTS13 allostery

When we cut ourselves, our blood must clot to stem the bleeding. However, if clotting takes place in a coronary artery it can cause a heart attack. These opposing life-saving and life-threatening consequences mean that strategies that target clotting to prevent heart attacks have to strike a very fine balance so as not to cause harm. Dr James Crawley and his team are studying an enzyme, ADAMTS13, that has potential to strike this balance. Blood clotting depends upon a type of blood cells called platelets, and a protein that circulates in the blood called VWF. The ability of VWF to recruit platelets to sites of injury is itself regulated by ADAMTS13 which can chop and inactivate VWF. Due to its important role in blood clotting, lower levels of ADAMTS13 increases the risk of heart attack and stroke. ADAMTS13 is a very promising potential anti-clotting drug because it is highly specific for VWF, which means that it could be used as a clot busting drug with less bleeding side effects compared to other currently available medicines. This project will establish at the molecular level how ADAMTS13 specifically recognises VWF, and how its activity is controlled. This could pave the way for development of ADAMTS13 as a safe clot buster for the treatment of heart attack and stroke.