@article{352dccc663b048039d2f5687e1993e94,
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 and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 . 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 GGGMPPCP to the GG transition-state complex identifies a hydrolysis-dependent powerstroke that may play a role in membrane-remodeling events necessary for fission.",
author = "Chappie, {Joshua S.} and Mears, {Jason A.} and Shunming Fang and Marilyn Leonard and Schmid, {Sandra L.} and Milligan, {Ronald A.} and Hinshaw, {Jenny E.} and Fred Dyda",
note = "Funding Information: We thank Vasyl Lukiyanchuk and Sharmistha Acharya for assistance in cloning and purification, Rodolfo Ghirlando for assistance with sedimentation velocity experiments, Juha-Pekka Mattila for communication of unpublished data, Joshua Zimmerberg for insightful discussions, Alison B. Hickman for technical advice and critical reading of the manuscript, and Yihong Ye for critical reading of the manuscript. We especially thank Marijn Ford and Jodi Nunnari for the ongoing open dialogue regarding the intricacies of dynamin structure and assembly. This work was supported by the Intramural Program of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and NIH grants GM52468 and GM75820 (to R.A.M.) and GM42455 (to S.L.S.). J.S.C. was supported by a Nancy Nossal Fellowship award from NIDDK. A portion of the work presented here was conducted at the National Resource for Automated Molecular Microscopy, which is supported by the National Institutes of Health through the National Center for Research Resources' P41 program (RR017573). ",
year = "2011",
month = sep,
day = "30",
doi = "10.1016/j.cell.2011.09.003",
language = "English (US)",
volume = "147",
pages = "209--222",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "1",
}