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Topological arrangement of the intracellular membrane fusion machinery

Soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) form a four-helix coiled-coil bundle that juxtaposes two bilayers and drives a basal level of membrane fusion. The Sec1/Munc18 (SM) protein binds to its cognate SNARE bundle and accelerates the basal fusion reaction. The...

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Detalles Bibliográficos
Autores principales: Rathore, Shailendra S., Ghosh, Nilanjan, Ouyang, Yan, Shen, Jingshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135485/
https://www.ncbi.nlm.nih.gov/pubmed/21633111
http://dx.doi.org/10.1091/mbc.E11-03-0190
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author Rathore, Shailendra S.
Ghosh, Nilanjan
Ouyang, Yan
Shen, Jingshi
author_facet Rathore, Shailendra S.
Ghosh, Nilanjan
Ouyang, Yan
Shen, Jingshi
author_sort Rathore, Shailendra S.
collection PubMed
description Soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) form a four-helix coiled-coil bundle that juxtaposes two bilayers and drives a basal level of membrane fusion. The Sec1/Munc18 (SM) protein binds to its cognate SNARE bundle and accelerates the basal fusion reaction. The question of how the topological arrangement of the SNARE helices affects the reactivity of the fusion proteins remains unanswered. Here we address the problem for the first time in a reconstituted system containing both SNAREs and SM proteins. We find that to be fusogenic a SNARE topology must support both basal fusion and SM stimulation. Certain topological combinations of exocytic SNAREs result in basal fusion but cannot support SM stimulation, whereas other topologies support SM stimulation without inducing basal fusion. It is striking that of all the possible topological combinations of exocytic SNARE helices, only one induces efficient fusion. Our results suggest that the intracellular membrane fusion complex is designed to fuse bilayers according to one genetically programmed topology.
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spelling pubmed-31354852011-09-30 Topological arrangement of the intracellular membrane fusion machinery Rathore, Shailendra S. Ghosh, Nilanjan Ouyang, Yan Shen, Jingshi Mol Biol Cell Articles Soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs) form a four-helix coiled-coil bundle that juxtaposes two bilayers and drives a basal level of membrane fusion. The Sec1/Munc18 (SM) protein binds to its cognate SNARE bundle and accelerates the basal fusion reaction. The question of how the topological arrangement of the SNARE helices affects the reactivity of the fusion proteins remains unanswered. Here we address the problem for the first time in a reconstituted system containing both SNAREs and SM proteins. We find that to be fusogenic a SNARE topology must support both basal fusion and SM stimulation. Certain topological combinations of exocytic SNAREs result in basal fusion but cannot support SM stimulation, whereas other topologies support SM stimulation without inducing basal fusion. It is striking that of all the possible topological combinations of exocytic SNARE helices, only one induces efficient fusion. Our results suggest that the intracellular membrane fusion complex is designed to fuse bilayers according to one genetically programmed topology. The American Society for Cell Biology 2011-07-15 /pmc/articles/PMC3135485/ /pubmed/21633111 http://dx.doi.org/10.1091/mbc.E11-03-0190 Text en © 2011 Rathore et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology.
spellingShingle Articles
Rathore, Shailendra S.
Ghosh, Nilanjan
Ouyang, Yan
Shen, Jingshi
Topological arrangement of the intracellular membrane fusion machinery
title Topological arrangement of the intracellular membrane fusion machinery
title_full Topological arrangement of the intracellular membrane fusion machinery
title_fullStr Topological arrangement of the intracellular membrane fusion machinery
title_full_unstemmed Topological arrangement of the intracellular membrane fusion machinery
title_short Topological arrangement of the intracellular membrane fusion machinery
title_sort topological arrangement of the intracellular membrane fusion machinery
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135485/
https://www.ncbi.nlm.nih.gov/pubmed/21633111
http://dx.doi.org/10.1091/mbc.E11-03-0190
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