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Structural studies on the membrane receptor p58-ERGIC-53

Final Activity Report Summary - ERGIC (Structural studies on the membrane receptor p58-ERGIC-53)

This project concerned the glycoprotein-recognising transport protein ERGIC-53 along the ER-Golgi secretory pathway. ERGIC-53 is known to be responsible for the specific transport of certain blood coagulation factors, and mutations in either ERGIC-53 or its co-activator protein MCFD2 lead to an inherited bleeding disorder due to defects in the blood coagulation system.

Here, we could show with purified proteins that ERGIC-53 and MCFD2 interact directly and that the complex is a high-affinity one. This result is rather surprising, as it was expected that such a transporter complex would rather be of transient nature. It could also be shown that the binding is calcium-dependent and that the carbohydrate binding domain of ERGIC-53 is both necessary and sufficient for binding. Mutations to the calcium-binding residues of MCFD2 disrupt the binding.