A Pseudoatomic Model of the Dynamin Polymer Identifies a Hydrolysis-Dependent Powerstroke

被引：169

作者：

Chappie, Joshua S. ^{[2
]}

Mears, Jason A. ^{[1
,3
]}

Fang, Shunming ^{[1
]}

Leonard, Marilyn ^{[4
]}

Schmid, Sandra L. ^{[4
]}

Milligan, Ronald A. ^{[4
]}

Hinshaw, Jenny E. ^{[1
]}

Dyda, Fred ^{[2
]}

机构：

[1] NIDDKD, Lab Cell Biochem & Biol, Bethesda, MD 20892 USA

[2] NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA

[3] Case Western Reserve Univ, Dept Pharmacol, Sch Med, Cleveland, OH 44106 USA

[4] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA

来源：

CELL | 2011年 / 147卷 / 01期

基金：

美国国家卫生研究院;

关键词：

CLATHRIN-MEDIATED ENDOCYTOSIS; PLECKSTRIN HOMOLOGY DOMAIN; CONFORMATIONAL-CHANGES; CRYSTAL-STRUCTURE; GTPASE ACTIVITY; STALK REGION; IN-VIVO; MEMBRANE; CONSTRICTION; MECHANISM;

D O I：

10.1016/j.cell.2011.09.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 angstrom and a fusion protein, GG, linking human dynamin 1's catalytic G domain to its GTPase effector domain (GED) at 2.2 angstrom. 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.

引用

页码：209 / 222

页数：14

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