RT Journal Article
SR Electronic
T1 Mechanistic insights into the SNARE complex disassembly
JF Science Advances
JO Sci Adv
FD American Association for the Advancement of Science
SP eaau8164
DO 10.1126/sciadv.aau8164
VO 5
IS 4
A1 Huang, Xuan
A1 Sun, Shan
A1 Wang, Xiaojing
A1 Fan, Fenghui
A1 Zhou, Qiang
A1 Lu, Shan
A1 Cao, Yong
A1 Wang, Qiu-Wen
A1 Dong, Meng-Qiu
A1 Yao, Jun
A1 Sui, Sen-Fang
YR 2019
UL http://advances.sciencemag.org/content/5/4/eaau8164.abstract
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.