DOI: 10.1073/pnas.1816495115
论文题名: Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex
作者: Sharma S. ; Lindau M.
刊名: Proceedings of the National Academy of Sciences of the United States of America
ISSN: 0027-8424
出版年: 2018
卷: 115, 期: 50 起始页码: 12751
结束页码: 12756
语种: 英语
英文关键词: Exocytosis
; Membrane fusion nanodisc
; Molecular dynamics
; Transmitter release
Scopus关键词: nanodisc
; SNARE protein
; synaptobrevin 2
; syntaxin 1A
; agents interacting with transmitter, hormone or drug receptors
; membrane protein
; mutant protein
; SNARE protein
; synaptobrevin 2
; syntaxin 1
; Article
; carboxy terminal sequence
; cell membrane
; cell structure
; cellular, subcellular and molecular biological phenomena and functions
; complex formation
; controlled study
; exocytosis
; fusion pore
; fusion pore formation
; hydrophilicity
; membrane fusion
; molecular dynamics
; neurotransmitter release
; phenomena and functions of biological membrane
; priority journal
; protein domain
; synapse vesicle
; chemical phenomena
; cytoplasm
; diaphragm
; metabolism
; nerve cell
; physiology
; structural model
; Cytoplasm
; Diaphragm
; Hydrophobic and Hydrophilic Interactions
; Membrane Fusion
; Membrane Proteins
; Models, Structural
; Mutant Proteins
; Neurons
; Neurotransmitter Agents
; Protein Domains
; SNARE Proteins
; Synaptic Vesicles
; Syntaxin 1
; Vesicle-Associated Membrane Protein 2
英文摘要: Release of neurotransmitters from synaptic vesicles begins with narrow fusion pore, the structure of which remains unresolved. T obtain a structural model of the fusion pore, we performed coarse grained molecular dynamics simulations of fusion between nanodisc and a planar bilayer bridged by four partially unzippe SNARE complexes. The simulations revealed that zipping of SNAR complexes pulls the polar C-terminal residues of the synaptobrevi 2 and syntaxin 1A transmembrane domains to form a hydrophili core between the two distal leaflets, inducing fusion pore forma tion. The estimated conductances of these fusion pores are in goo agreement with experimental values. Two SNARE protein mutant inhibiting fusion experimentally produced no fusion pore forma tion. In simulations in which the nanodisc was replaced by a 40-nm vesicle, an extended hemifusion diaphragm formed but a fusio pore did not, indicating that restricted SNARE mobility is require for rapid fusion pore formation. Accordingly, rapid fusion por formation also occurred in the 40-nm vesicle system when SNAR mobility was restricted by external forces. Removal of the restrictio is required for fusion pore expansion. © 2018 National Academy of Sciences. All rights reserved. Citation statistics:
资源类型: 期刊论文
标识符: http://119.78.100.158/handle/2HF3EXSE/163630
Appears in Collections: 气候变化与战略
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作者单位: Sharma, S., Laboratory for Nanoscale Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, 37077, Germany; Lindau, M., Laboratory for Nanoscale Cell Biology, Max Planck Institute for Biophysical Chemistry, Göttingen, 37077, Germany, School of Applied and Engineering Physics, Cornell University, Ithaca, NY 14850, United States
Recommended Citation:
Sharma S.,Lindau M.. Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex[J]. Proceedings of the National Academy of Sciences of the United States of America,2018-01-01,115(50)