title: Nucleotide-dependent conformational changes in dynamin: evidence for a mechanochemical molecular spring.
abstract: The GTPase dynamin plays an essential part in endocytosis by catalysing the fission of nascent clathrin-coated vesicles from the plasma membrane. Using preformed phosphatidylinositol-4,5-bisphosphate-containing lipid nanotubes as a membrane template for dynamin self-assembly, we investigate the conformational changes that arise during GTP hydrolysis by dynamin. Electron microscopy reveals that, in the GTP-bound state, dynamin rings appear to be tightly packed together. After GTP hydrolysis, the spacing between rings increases nearly twofold. When bound to the nanotubes, dynamin's GTPase activity is cooperative and is increased by three orders of magnitude compared with the activity of unbound dynamin. An increase in the Kcat (but not the K(m) of GTP hydrolysis accounts for the pronounced cooperativity. These data indicate that a novel, lengthwise ('spring-like') conformational change in a dynamin helix may participate in vesicle fission.
authors.affiliation: MRC Laboratory of Molecular Biology, Cambridge, UK.
authors.forename: M H
authors.initials: MH
authors.lastname: Stowell
authors.forename: B
authors.initials: B
authors.lastname: Marks
authors.forename: P
authors.initials: P
authors.lastname: Wigge
authors.forename: H T
authors.initials: HT
authors.lastname: McMahon
mesh_terms: D000818:Animals; D001923:Brain Chemistry; D034281:Dynamins; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000737:chemistry* / Q000378:metabolism* / Q000648:ultrastructure; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008081:Liposomes; D008954:Models, Biological; D008958:Models, Molecular; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats
chemical_list: D008081:Liposomes; D019269:Phosphatidylinositol 4,5-Diphosphate; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D020558:GTP Phosphohydrolases; D034281:Dynamins