The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins.
Voltage dependence of fusion induced by class II and class III viral fusion proteins was investigated. Class II proteins from Ross River and Sindbus virus and a mutant class III protein from Epstein Barr virus were found to induce cell-cell fusion that is voltage dependent. Combined with previous st...
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doaj-8d88b327755d4b0bb81dd9812ed95d982020-11-25T01:52:50ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01810e7617410.1371/journal.pone.0076174The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins.Ruben M MarkosyanFredric S CohenVoltage dependence of fusion induced by class II and class III viral fusion proteins was investigated. Class II proteins from Ross River and Sindbus virus and a mutant class III protein from Epstein Barr virus were found to induce cell-cell fusion that is voltage dependent. Combined with previous studies, in all, four class II and two class III protein have now been shown to exhibit voltage-dependent fusion, demonstrating that this is probably a general phenomenon for these two classes of viral fusion proteins. In the present study, monitoring fusion of pseudovirus expressing Vesicular Stomatitis virus (VSV) G within endosomes shows that here, too, fusion is voltage dependent. This supports the claim that voltage dependence of fusion is biologically relevant and that cell-cell fusion reliably models the voltage dependence. Fusion induced by class I viral proteins is independent of voltage; chimeras expressing the ectodomain of a class I fusion protein and the transmembrane domain of VSV G could therefore be used to explore the location within the protein responsible for voltage dependence. Results showed that the transmembrane domain is the region associated with voltage dependence. Experiments in which cells were enriched with acidic lipids led to the conclusion that it is the flip-flop of acidic lipids that carries the charge responsible for the observed voltage dependence of fusion. This flip-flop occurred downstream of hemifusion, in accord with previous findings that the voltage dependent steps of fusion occur at a stage subsequent to hemifusion.http://europepmc.org/articles/PMC3790697?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ruben M Markosyan Fredric S Cohen |
spellingShingle |
Ruben M Markosyan Fredric S Cohen The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins. PLoS ONE |
author_facet |
Ruben M Markosyan Fredric S Cohen |
author_sort |
Ruben M Markosyan |
title |
The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins. |
title_short |
The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins. |
title_full |
The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins. |
title_fullStr |
The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins. |
title_full_unstemmed |
The transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class II and III viral proteins. |
title_sort |
transmembrane domain and acidic lipid flip-flop regulates voltage-dependent fusion mediated by class ii and iii viral proteins. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2013-01-01 |
description |
Voltage dependence of fusion induced by class II and class III viral fusion proteins was investigated. Class II proteins from Ross River and Sindbus virus and a mutant class III protein from Epstein Barr virus were found to induce cell-cell fusion that is voltage dependent. Combined with previous studies, in all, four class II and two class III protein have now been shown to exhibit voltage-dependent fusion, demonstrating that this is probably a general phenomenon for these two classes of viral fusion proteins. In the present study, monitoring fusion of pseudovirus expressing Vesicular Stomatitis virus (VSV) G within endosomes shows that here, too, fusion is voltage dependent. This supports the claim that voltage dependence of fusion is biologically relevant and that cell-cell fusion reliably models the voltage dependence. Fusion induced by class I viral proteins is independent of voltage; chimeras expressing the ectodomain of a class I fusion protein and the transmembrane domain of VSV G could therefore be used to explore the location within the protein responsible for voltage dependence. Results showed that the transmembrane domain is the region associated with voltage dependence. Experiments in which cells were enriched with acidic lipids led to the conclusion that it is the flip-flop of acidic lipids that carries the charge responsible for the observed voltage dependence of fusion. This flip-flop occurred downstream of hemifusion, in accord with previous findings that the voltage dependent steps of fusion occur at a stage subsequent to hemifusion. |
url |
http://europepmc.org/articles/PMC3790697?pdf=render |
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