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

Author

Listed:
  • Chuchu Wang

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Jia Tu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shengnan Zhang

    (Chinese Academy of Sciences)

  • Bin Cai

    (University of Cincinnati College of Medicine)

  • Zhenying Liu

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Shouqiao Hou

    (Chinese Academy of Sciences
    University of Chinese Academy of Sciences)

  • Qinglu Zhong

    (Chinese Academy of Sciences)

  • Xiao Hu

    (University of Cincinnati College of Medicine)

  • Wenbin Liu

    (Chinese Academy of Sciences)

  • Guohui Li

    (Chinese Academy of Sciences)

  • Zhijun Liu

    (Chinese Academy of Sciences)

  • Lin He

    (Shanghai Jiao Tong University)

  • Jiajie Diao

    (University of Cincinnati College of Medicine)

  • Zheng-Jiang Zhu

    (Chinese Academy of Sciences)

  • Dan Li

    (Shanghai Jiao Tong University
    Shanghai Jiao Tong University)

  • Cong Liu

    (Chinese Academy of Sciences)

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.

Suggested Citation

  • Chuchu Wang & Jia Tu & Shengnan Zhang & Bin Cai & Zhenying Liu & Shouqiao Hou & Qinglu Zhong & Xiao Hu & Wenbin Liu & Guohui Li & Zhijun Liu & Lin He & Jiajie Diao & Zheng-Jiang Zhu & Dan Li & Cong Li, 2020. "Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-15270-4
    DOI: 10.1038/s41467-020-15270-4
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