Crystal structure of nucleotide-free dynamin

Dynamin is a mechanochemical GTPase that oligomerizes around the neck of clathrin-coated pits and catalyses vesicle scission in a GTP-hydrolysis-dependent manner. The molecular details of oligomerization and the mechanism of the mechanochemical coupling are currently unknown. Here we present the crystal structure of human dynamin 1 in the nucleotide-free state with a four-domain architecture comprising the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin 1 oligomerized in the crystals via the stalks, which assemble in a criss-cross fashion. The stalks further interact via conserved surfaces with the pleckstrin homology domain and the bundle signalling element of the neighbouring dynamin molecule. This intricate domain interaction rationalizes a number of disease-related mutations in dynamin 2 and suggests a structural model for the mechanochemical coupling that reconciles previous models of dynamin function. Dynamin structure and function Dynamin is a GTPase that catalyses vesicle scission during clathrin-mediated endocytosis. Two related studies present the crystal structure of dynamin 1, including the GTPase domain, the bundle signalling element, the stalk and the pleckstrin homology domain. Dynamin-related proteins are ubiquitous regulators of membrane shape, and these structures provide insights into the mechanisms of dynamin 1 self-assembly and membrane scission events.