Crystal structure of the GTPase domain and the bundle signalling element of dynamin in the GDP state

Abstract

Dynamin is the prototype of a family of large multi-domain GTPases. The 100 kDa protein is a key playerin clathrin-mediated endocytosis, where it cleaves off vesicles from membranes using the energy fromGTP hydrolysis. We have solved the high resolution crystal structure of a fusion protein of the GTPasedomain and the bundle signalling element (BSE) of dynamin 1 liganded with GDP. The structure providesa hitherto missing snapshot of the GDP state of the hydrolytic cycle of dynamin and reveals how theswitch I region moves away from the active site after GTP hydrolysis and release of inorganic phosphate.Comparing our structure of the GDP state with the known structures of the GTP state, the transition stateand the nucleotide-free state of dynamin 1 we describe the structural changes through the hydrolyticcycle