UCSF

The family of dynamin fission proteins polymerize and use GTP to divide eukaryotic membranous structures including endocytic necks, peroxisomes, mitochondria, chloroplasts, and plastids. Current models for how fission dynamins constrict and divide membranes describe cleavage of budding endocytic vesicles. However, the mechanisms by which dynamins can divide the larger, low-curvature membranes of entire organelles remain poorly understood. Here we report cryo-EM structures of polymers of the human mitochondrial fission dynamin-related protein 1 (DRP1) stabilized in high- and low- curvature states at 3.5-4 Å resolution. Together these reveal the structural determinants by which DRP1 is adapted to the larger diameter of the mitochondria, and a unique mechanism of constriction that allows DRP1 to constrict low curvature membranes to the size of endocytic necks without GTP hydrolysis. These adaptations of metazoan DRP1 proteins are localized to the canonical dynamin interface 1 and the interface between the Stalk domain and the Bundle-Signaling Element. These results suggest that tuning of these two interfaces allow different members of the fission dynamin family to constrict not only endocytic necks, but also a diversity of eukaryotic membrane-bound organelles.