title: A pseudoatomic model of the dynamin polymer identifies a hydrolysis-dependent powerstroke.
abstract: The GTPase dynamin catalyzes membrane fission by forming a collar around the necks of clathrin-coated pits, but the specific structural interactions and conformational changes that drive this process remain a mystery. We present the GMPPCP-bound structures of the truncated human dynamin 1 helical polymer at 12.2 Å and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 Å. The structures reveal the position and connectivity of dynamin fragments in the assembled structure, showing that G domain dimers only form between tetramers in sequential rungs of the dynamin helix. Using chemical crosslinking, we demonstrate that dynamin tetramers are made of two dimers, in which the G domain of one molecule interacts in trans with the GED of another. Structural comparison of GG(GMPPCP) to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.
authors.affiliation: Laboratory of Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Chappie
authors.forename: Jason A
authors.initials: JA
authors.lastname: Mears
authors.forename: Shunming
authors.initials: S
authors.lastname: Fang
authors.forename: Marilyn
authors.initials: M
authors.lastname: Leonard
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Schmid
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Milligan
authors.forename: Jenny E
authors.initials: JE
authors.lastname: Hinshaw
authors.forename: Fred
authors.initials: F
authors.lastname: Dyda
mesh_terms: D018360:Crystallography, X-Ray; D034284:Dynamin I / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis; D008958:Models, Molecular; D017434:Protein Structure, Tertiary
chemical_list: D034284:Dynamin I