title: Invited review: Mechanisms of GTP hydrolysis and conformational transitions in the dynamin superfamily.
abstract: Dynamin superfamily proteins are multidomain mechano-chemical GTPases which are implicated in nucleotide-dependent membrane remodeling events. A prominent feature of these proteins is their assembly- stimulated mechanism of GTP hydrolysis. The molecular basis for this reaction has been initially clarified for the dynamin-related guanylate binding protein 1 (GBP1) and involves the transient dimerization of the GTPase domains in a parallel head-to-head fashion. A catalytic arginine finger from the phosphate binding (P-) loop is repositioned toward the nucleotide of the same molecule to stabilize the transition state of GTP hydrolysis. Dynamin uses a related dimerization-dependent mechanism, but instead of the catalytic arginine, a monovalent cation is involved in catalysis. Still another variation of the GTP hydrolysis mechanism has been revealed for the dynamin-like Irga6 which bears a glycine at the corresponding position in the P-loop. Here, we highlight conserved and divergent features of GTP hydrolysis in dynamin superfamily proteins and show how nucleotide binding and hydrolysis are converted into mechano-chemical movements. We also describe models how the energy of GTP hydrolysis can be harnessed for diverse membrane remodeling events, such as membrane fission or fusion. © 2016 Wiley Periodicals, Inc. Biopolymers 105: 580-593, 2016.
authors.affiliation: Kristallographie, Max-Delbrück Centrum Für Molekulare Medizin, Robert-Rössle-Straße 10, Berlin, 13125, Germany.|Institut Für Chemie und Biochemie, Freie Universität Berlin, Takustraße 3, Berlin, 14195, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Daumke
authors.affiliation: Abteilung Hämatologie/Transfusionsmedizin, Paul-Ehrlich-Institut, Paul-Ehrlich-Straße 51-59, Langen, 63225, Germany.
authors.forename: Gerrit J K
authors.initials: GJ
authors.lastname: Praefcke
mesh_terms: D000818:Animals; D034281:Dynamins / Q000737:chemistry* / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006868:Hydrolysis; D008956:Models, Chemical; D000072417:Protein Domains; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: C490287:GBP1 protein, human; D006160:Guanosine Triphosphate; D019204:GTP-Binding Proteins; D034281:Dynamins
keywords: GTPases; catalytic mechanism; dynamin; mechanochemical enzyme; structural biology