The role of the N-D1 linker of the N-ethylmaleimide-sensitive factor in the SNARE disassembly.
The role of the N-D1 linker of the N-ethylmaleimide-sensitive factor in the SNARE disassembly.
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N-乙基马来酰亚胺敏感因子的 N-D1 连接子在 SNARE 拆卸中的作用
DOI：
10.1371/journal.pone.0064346
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sui SF
中科院分区：
文献类型：
--
作者：
Liu CC;Sun S;Sui SF
N-ethylmaleimide-sensitive factor (NSF) is a member of the type II AAA+ (ATPase associated with various cellular activities) family. It plays a critical role in intracellular membrane trafficking by disassembling soluble NSF attachment protein receptor (SNARE) complexes. Each NSF protomer consists of an N-terminal domain (N domain) followed by two AAA ATPase domains (D1 and D2) in tandem. The N domain is required for SNARE/α-SNAP binding and the D1 domain accounts for the majority of ATP hydrolysis. Little is known about the role of the N-D1 linker in the NSF function. This study presents detailed mutagenesis analyses of NSF N-D1 linker, dissecting its role in the SNARE disassembly, the SNARE/α-SNAP complex binding, the basal ATPase activity and the SNARE/α-SNAP stimulated ATPase activity. Our results show that the N-terminal region of the N-D1 linker associated mutants cause severe defect in SNARE complex disassembly, but little effects on the SNARE/α-SNAP complex binding, the basal and the SNARE/α-SNAP stimulated ATPase activity, suggesting this region may be involved in the motion transmission from D1 to N domain. Mutating the residues in middle and C-terminal region of the N-D1 linker increases the basal ATPase activity, indicating it may play a role in autoinhibiting NSF activity until it encounters SNARE/α-SNAP complex substrate. Moreover, mutations at the C-terminal sequence GIGG exhibit completely abolished or severely reduced activities of the substrate binding, suggesting that the flexibility of N-D1 linker is critical for the movement of the N domain that is required for the substrate binding. Taken together, these data suggest that the whole N-D1 linker is critical for the biological function of NSF to disassemble SNARE complex substrate with different regions responsible for different roles.
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影响因子：
64.8
作者：
SOLLNER, T;WHITEHART, SW;ROTHMAN, JE
通讯作者：
ROTHMAN, JE
影响因子：
4.8
作者：
Matveeva, EA;He, P;Whiteheart, SW
通讯作者：
Whiteheart, SW
影响因子：
64.8
作者：
Stein, Alexander;Weber, Gert;Wahl, Markus C.;Jahn, Reinhard
通讯作者：
Jahn, Reinhard
影响因子：
3
作者：
Smith, GR;Contreras-Moreira, B;Bates, PA
通讯作者：
Bates, PA
N-域在哺乳动物AAA ATPase P97/VCP的ATPase活性中的作用。
DOI：
10.1074/jbc.m111.302778
发表时间：
2012-03-09
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Niwa H;Ewens CA;Tsang C;Yeung HO;Zhang X;Freemont PS
通讯作者：
Freemont PS