Metabolomics

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Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly


ABSTRACT: Vesicle associated membrane protein 2 (VAMP2/synaptobrevin2), a core SNARE protein residing on synaptic vesicles (SVs), forms helix bundles with syntaxin-1 and SNAP25 for the SNARE assembly. Prior to the SNARE assembly, the structure of VAMP2 is unclear. Here, by using in-cell NMR spectroscopy, we describe the dynamic membrane association of VAMP2 SNARE motif in mammalian cells, and the structural change of VAMP2 upon the change of intracellular lipid environment. We analyze the lipid compositions of the SV membrane by mass-spectrometry-based lipidomic profiling, and further reveal that VAMP2 forms distinctive conformations in different membrane regions. In contrast to the non-raft region, the membrane region of cholesterol-rich lipid raft markedly weakens the membrane association of VAMP2 SNARE motif, which releases the SNARE motif and facilitates the SNARE assembly. Our work reveals the regulation of different membrane regions on VAMP2 structure and sheds light on the spatial regulation of SNARE assembly.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse phase, Liquid Chromatography MS - positive - reverse phase

SUBMITTER: Xiaotao Shen 

PROVIDER: MTBLS1503 | MetaboLights | 2021-10-06

REPOSITORIES: MetaboLights

Dataset's files

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Action DRS
MTBLS1503 Other
FILES Other
a_MTBLS1503_LC-MS_negative_reverse-phase_metabolite_profiling.txt Txt
a_MTBLS1503_LC-MS_positive_reverse-phase_metabolite_profiling.txt Txt
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Publications

Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly.

Wang Chuchu C   Tu Jia J   Zhang Shengnan S   Cai Bin B   Liu Zhenying Z   Hou Shouqiao S   Zhong Qinglu Q   Hu Xiao X   Liu Wenbin W   Li Guohui G   Liu Zhijun Z   He Lin L   Diao Jiajie J   Zhu Zheng-Jiang ZJ   Li Dan D   Liu Cong C  

Nature communications 20200324 1


Vesicle associated membrane protein 2 (VAMP2/synaptobrevin2), a core SNARE protein residing on synaptic vesicles (SVs), forms helix bundles with syntaxin-1 and SNAP25 for the SNARE assembly. Prior to the SNARE assembly, the structure of VAMP2 is unclear. Here, by using in-cell NMR spectroscopy, we describe the dynamic membrane association of VAMP2 SNARE motif in mammalian cells, and the structural change of VAMP2 upon the change of intracellular lipid environment. We analyze the lipid compositio  ...[more]

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