A dynamin mutant defines a superconstricted prefission state

Anna C. Sundborger, Shunming Fang, Jürgen A. Heymann, Pampa Ray, Joshua S. Chappie, Jenny E. Hinshaw

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Dynamin is a 100 kDa GTPase that organizes into helical assemblies at the base of nascent clathrincoated vesicles. Formation of these oligomers stimulates the intrinsic GTPase activity of dynamin, which is necessary for efficient membrane fission during endocytosis. Recent evidence suggests that the transition state of dynamin's GTP hydrolysis reaction serves as a key determinant of productive fission. Here, we present the structure of a transition- state-defective dynamin mutant K44A trapped in a prefission state at 12.5 Å resolution. This structure constricts to 3.7 nm, reaching the theoretical limit required for spontaneous membrane fission. Computational docking indicates that the groundstate conformation of the dynamin polymer is sufficient to achieve this superconstricted prefission state and reveals how a two-start helical symmetry promotes the most efficient packing of dynamin tetramers around the membrane neck. These data suggest a model for the assembly and regulation of the minimal dynamin fission machine.

Original languageEnglish (US)
Pages (from-to)734-742
Number of pages9
JournalCell reports
Volume8
Issue number3
DOIs
StatePublished - Aug 7 2014

Bibliographical note

Funding Information:
This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. J.S.C. is a Nancy and Peter Meinig Family Investigator in the Life Sciences. We thank Drs. Naiqian Cheng and Dennis Winkler for technical assistance on the FEI Polara; Drs. Jeanne Morin-Leisk, Paula Flicker, and Toshi Kawate for insightful discussions; and Dr. Fred Dyda for his continued support and generosity.

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