气候变化领域集成服务门户(CCPortal): Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex

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DOI	10.1073/pnas.1816495115
	Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex
	Sharma S.; Lindau M.
发表日期	2018
ISSN	0027-8424
起始页码	12751
结束页码	12756
卷号	115 期号:50
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.
英文关键词	Exocytosis; Membrane fusion nanodisc; Molecular dynamics; Transmitter release
语种	英语
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
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/160437
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
推荐引用方式 GB/T 7714	Sharma S.,Lindau M.. Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex[J],2018,115(50).
APA	Sharma S.,&Lindau M..(2018).Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex.Proceedings of the National Academy of Sciences of the United States of America,115(50).
MLA	Sharma S.,et al."Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex".Proceedings of the National Academy of Sciences of the United States of America 115.50(2018).