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 trafficking events in the Golgi all require dynamin for vesiculation. The dynamin-related protein Drp1 (Dlp1) has been implicated in mitochondria fission and a plant dynamin-like protein phragmoplastin is involved in the vesicular events leading to cell wall formation. A common theme among these proteins is their ability to self-assemble into spirals and their localization to areas of membrane fission. Here we present the first three-dimensional structure of dynamin at a resolution of approximately 20 A, determined from cryo-electron micrographs of tubular crystals in the constricted state. The map reveals a T-shaped dimer consisting of three prominent densities: leg, stalk and head. The structure suggests that the dense stalk and head regions rearrange when GTP is added, a rearrangement that generates a force on the underlying lipid bilayer and thereby leads to membrane constriction. These results indicate that dynamin is a force-generating 'contrictase'.
Zhang
P
P
Laboratory of Cell Biochemistry and Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Building 8, Room 419, MSC 0851, 8 Center Drive, National Institutes of Health, Bethesda, Maryland 20892, USA.
Hinshaw
J E
JE
D000818:Animals; D001665:Binding Sites; D020285:Cryoelectron Microscopy; D003460:Crystallization; D019281:Dimerization; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D006160:Guanosine Triphosphate / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D008051:Lipid Bilayers; D008081:Liposomes / Q000378:metabolism; D008854:Microscopy, Electron; D008958:Models, Molecular; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
D008051:Lipid Bilayers; D008081:Liposomes; D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D034281:Dynamins