A tethering complex drives the terminal stage of SNARE-dependent membrane fusion.

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Version: Author's accepted manuscript
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Serval ID
serval:BIB_6712BB1A30F8
Type
Article: article from journal or magazin.
Collection
Publications
Title
A tethering complex drives the terminal stage of SNARE-dependent membrane fusion.
Journal
Nature
Author(s)
D'Agostino M., Risselada H.J., Lürick A., Ungermann C., Mayer A.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Publication state
Published
Issued date
30/11/2017
Peer-reviewed
Oui
Volume
551
Number
7682
Pages
634-638
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Membrane fusion in eukaryotic cells mediates the biogenesis of organelles, vesicular traffic between them, and exo- and endocytosis of important signalling molecules, such as hormones and neurotransmitters. Distinct tasks in intracellular membrane fusion have been assigned to conserved protein systems. Tethering proteins mediate the initial recognition and attachment of membranes, whereas SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) protein complexes are considered as the core fusion engine. SNARE complexes provide mechanical energy to distort membranes and drive them through a hemifusion intermediate towards the formation of a fusion pore. This last step is highly energy-demanding. Here we combine the in vivo and in vitro fusion of yeast vacuoles with molecular simulations to show that tethering proteins are critical for overcoming the final energy barrier to fusion pore formation. SNAREs alone drive vacuoles only into the hemifused state. Tethering proteins greatly increase the volume of SNARE complexes and deform the site of hemifusion, which lowers the energy barrier for pore opening and provides the driving force. Thereby, tethering proteins assume a crucial mechanical role in the terminal stage of membrane fusion that is likely to be conserved at multiple steps of vesicular traffic. We therefore propose that SNAREs and tethering proteins should be considered as a single, non-dissociable device that drives fusion. The core fusion machinery may then be larger and more complex than previously thought.
Keywords
Ligands, Membrane Fusion, Molecular Dynamics Simulation, SNARE Proteins/metabolism, Saccharomyces cerevisiae/cytology, Saccharomyces cerevisiae/metabolism, Saccharomyces cerevisiae Proteins/metabolism, Synaptosomal-Associated Protein 25/metabolism, Vacuoles/metabolism
Pubmed
Web of science
Create date
06/12/2017 14:34
Last modification date
30/11/2019 7:09
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