Determining the conformational changes of multi-domain adaptor proteins driving clathrin mediated endocytosis

Clathrin-mediated endocytosis (CME) is driven by the assembly of adaptor proteins that participate in cargo selection, clathrin recruitment and membrane bending. Eps15, Dab2 and FCHo1/2 are early initiators of CME and they work together to recruit the adaptor proteins that drive vesicle formation. Multivalent interactions through both folded domains and intrinsically disordered regions of these proteins facilitate an interconnected protein network, that triggers the formation of biological condensates. However, the molecular details of both the interactions and domain reorganization are still unkown. Using NMR spectroscopy, we have unveiled the local structure and the interaction modes of these proteins, suggesting the presence of long-range contacts affecting the global conformations. Therefore, we aim to understand the global conformational changes occurring within Eps15, FCHo1/2 and Dab2 proteins during the initiation of CME and how they relate to liquid-liquid phase separation.