PT  - JOURNAL ARTICLE
AU  - Huang, Xuan
AU  - Sun, Shan
AU  - Wang, Xiaojing
AU  - Fan, Fenghui
AU  - Zhou, Qiang
AU  - Lu, Shan
AU  - Cao, Yong
AU  - Wang, Qiu-Wen
AU  - Dong, Meng-Qiu
AU  - Yao, Jun
AU  - Sui, Sen-Fang
TI  - Mechanistic insights into the SNARE complex disassembly
AID  - 10.1126/sciadv.aau8164
DP  - 2019 Apr 01
TA  - Science Advances
PG  - eaau8164
VI  - 5
IP  - 4
4099  - http://advances.sciencemag.org/content/5/4/eaau8164.short
4100  - http://advances.sciencemag.org/content/5/4/eaau8164.full
SO  - Sci Adv2019 Apr 01; 5
AB  - NSF (N-ethylmaleimide–sensitive factor) and α-SNAP (α–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 α-SNAP–SNARE subcomplex and the NSF-D1D2 domain in the 20S complex at 3.9- and 3.7-Å resolutions, respectively. Combined with the biochemical and electrophysiological analyses, we find that α-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 α-SNAP–mediated disassembly of the SNARE complex.