title: Crystal structure of nucleotide-free dynamin.
abstract: 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.
authors.affiliation: Crystallography, Max-Delbrück-Centrum for Molecular Medicine, Robert-Rössle-Strasse 10, 13125 Berlin, Germany. katja.faelber@mdc-berlin.de
authors.forename: Katja
authors.initials: K
authors.lastname: Faelber
authors.forename: York
authors.initials: Y
authors.lastname: Posor
authors.forename: Song
authors.initials: S
authors.lastname: Gao
authors.forename: Martin
authors.initials: M
authors.lastname: Held
authors.forename: Yvette
authors.initials: Y
authors.lastname: Roske
authors.forename: Dennis
authors.initials: D
authors.lastname: Schulze
authors.forename: Volker
authors.initials: V
authors.lastname: Haucke
authors.forename: Frank
authors.initials: F
authors.lastname: Noé
authors.forename: Oliver
authors.initials: O
authors.lastname: Daumke
mesh_terms: D018360:Crystallography, X-Ray; D034284:Dynamin I / Q000737:chemistry* / Q000378:metabolism; D034285:Dynamin II / Q000235:genetics / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009711:Nucleotides; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014168:Transferrin / Q000378:metabolism
chemical_list: D009711:Nucleotides; D014168:Transferrin; D006160:Guanosine Triphosphate; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034285:Dynamin II