Three-dimensional reconstruction of dynamin in the constricted state

Members of the dynamin family of GTPases have unique structural properties that might reveal a general mechanochemical basis for membrane constriction . Receptor-mediated endocytosis, caveolae internalization and certain traff icking events in the Golgi all require dynamin for vesiculation(1). The dyn amin-related protein Drp1 (Dlp1) has been implicated in mitochondria fissio n(2) and a plant dynamin-like protein phragmoplastin is involved in the ves icular events leading to cell wall formation(3). A common theme among these proteins is their ability to self-assemble into spirals and their localiza tion to areas of membrane fission. Here we present the first three-dimensio nal structure of dynamin at a resolution of similar to 20 Angstrom, determi ned from cryo-electron micrographs of tubular crystals in the constricted s tate. The map reveals a T-shaped dimer consisting of three prominent densit ies: leg, stalk and head. The structure suggests that the dense stalk and h ead regions rearrange when GTP is added, a rearrangement that generates a f orce on the underlying lipid bilayer and thereby leads to membrane constric tion. These results indicate that dynamin is a force-generating 'contrictas e'.