Mechanistic insights into the SNARE complex disassembly

被引：33

作者：

Huang, Xuan ^{[1
,4
]}

Sun, Shan ^{[1
]}

Wang, Xiaojing ^{[1
]}

Fan, Fenghui ^{[1
]}

Zhou, Qiang ^{[1
,5
]}

Lu, Shan ^{[2
]}

Cao, Yong ^{[2
]}

Wang, Qiu-Wen ^{[3
]}

Dong, Meng-Qiu ^{[2
]}

Yao, Jun ^{[3
]}

Sui, Sen-Fang ^{[1
]}

机构：

[1] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Life Sci, State Key Lab Membrane Biol, Beijing 100084, Peoples R China

[2] Natl Inst Biol Sci, Beijing 102206, Peoples R China

[3] Tsinghua Univ, IDG McGovern Inst Brain Res, Sch Life Sci, State Key Lab Membrane Biol,Tsinghua Peking Joint, Beijing 100084, Peoples R China

[4] Capital Med Univ, Beijing Chaoyang Hosp, Med Res Ctr, Beijing 100020, Peoples R China

[5] Tsinghua Univ, Beijing Adv Innovat Ctr Struct Biol, Sch Med, State Key Lab Membrane Biol, Beijing 100084, Peoples R China

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 04期

基金：

中国国家自然科学基金;

关键词：

BEAM-INDUCED MOTION; CRYO-EM STRUCTURE; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; FUSION; NSF; DOCKING; SYSTEM;

D O I：

10.1126/sciadv.aau8164

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

NSF (N-ethylmaleimide-sensitive factor) and alpha-SNAP (alpha-soluble NSF attachment protein) bind to the SNARE (soluble NSF attachment protein receptor) complex, the minimum machinery to mediate membrane fusion, to form a 20S complex, which disassembles the SNARE complex for reuse. We report the cryo-EM structures of the alpha-SNAP-SNARE subcomplex and the NSF-D1D2 domain in the 20S complex at 3.9- and 3.7-angstrom resolutions, respectively. Combined with the biochemical and electrophysiological analyses, we find that alpha-SNAPs use R116 through electrostatic interactions and L197 through hydrophobic interactions to apply force mainly on two positions of the VAMP protein to execute disassembly process. Furthermore, we define the interaction between the amino terminus of the SNARE helical bundle and the pore loop of the NSF-D1 domain and demonstrate its essential role as a potential anchor for SNARE complex disassembly. Our studies provide a rotation model of alpha-SNAP-mediated disassembly of the SNARE complex.

引用

页数：11

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