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  Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex.

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), 12751-12756. doi:10.1073/pnas.1816495115.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-971A-7 Version Permalink: http://hdl.handle.net/21.11116/0000-0003-B90A-2
Genre: Journal Article

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 Creators:
Sharma, S.1, Author              
Lindau, M.1, Author              
Affiliations:
1Research Group of Nanoscale Cell Biology, MPI for Biophysical Chemistry, Max Planck Society, ou_1832294              

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Free keywords: exocytosis; membrane fusion; molecular dynamics; nanodisc; transmitter release
 Abstract: Release of neurotransmitters from synaptic vesicles begins with a narrow fusion pore, the structure of which remains unresolved. To obtain a structural model of the fusion pore, we performed coarse-grained molecular dynamics simulations of fusion between a nanodisc and a planar bilayer bridged by four partially unzipped SNARE complexes. The simulations revealed that zipping of SNARE complexes pulls the polar C-terminal residues of the synaptobrevin 2 and syntaxin 1A transmembrane domains to form a hydrophilic core between the two distal leaflets, inducing fusion pore formation. The estimated conductances of these fusion pores are in good agreement with experimental values. Two SNARE protein mutants inhibiting fusion experimentally produced no fusion pore formation. In simulations in which the nanodisc was replaced by a 40-nm vesicle, an extended hemifusion diaphragm formed but a fusion pore did not, indicating that restricted SNARE mobility is required for rapid fusion pore formation. Accordingly, rapid fusion pore formation also occurred in the 40-nm vesicle system when SNARE mobility was restricted by external forces. Removal of the restriction is required for fusion pore expansion.

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Language(s): eng - English
 Dates: 2018-12-112018-11-27
 Publication Status: Published online
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 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1073/pnas.1816495115
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Title: Proceedings of the National Academy of Sciences of the United States of America
Source Genre: Journal
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Pages: - Volume / Issue: 115 (50) Sequence Number: - Start / End Page: 12751 - 12756 Identifier: -