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Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion

Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. During fusion, these class II viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain III and stem regions f...

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Detalles Bibliográficos
Autores principales: Liao, Maofu, Kielian, Margaret
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2005
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171229/
https://www.ncbi.nlm.nih.gov/pubmed/16216925
http://dx.doi.org/10.1083/jcb.200507075
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author Liao, Maofu
Kielian, Margaret
author_facet Liao, Maofu
Kielian, Margaret
author_sort Liao, Maofu
collection PubMed
description Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. During fusion, these class II viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain III and stem regions folded back toward the target membrane-inserted fusion peptides. We demonstrate that exogenous domain III can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and infection. Domain III binds stably to the fusion protein, thus preventing the foldback reaction and blocking the lipid mixing step of fusion. Our data reveal the existence of a relatively long-lived core trimer intermediate with which domain III interacts to initiate membrane fusion. These novel inhibitors of the class II fusion proteins show cross-inhibition within the virus genus and suggest that the domain III–core trimer interaction can serve as a new target for the development of antiviral reagents.
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spelling pubmed-21712292008-03-05 Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion Liao, Maofu Kielian, Margaret J Cell Biol Research Articles Alphaviruses and flaviviruses infect cells through low pH-dependent membrane fusion reactions mediated by their structurally similar viral fusion proteins. During fusion, these class II viral fusion proteins trimerize and refold to form hairpin-like structures, with the domain III and stem regions folded back toward the target membrane-inserted fusion peptides. We demonstrate that exogenous domain III can function as a dominant-negative inhibitor of alphavirus and flavivirus membrane fusion and infection. Domain III binds stably to the fusion protein, thus preventing the foldback reaction and blocking the lipid mixing step of fusion. Our data reveal the existence of a relatively long-lived core trimer intermediate with which domain III interacts to initiate membrane fusion. These novel inhibitors of the class II fusion proteins show cross-inhibition within the virus genus and suggest that the domain III–core trimer interaction can serve as a new target for the development of antiviral reagents. The Rockefeller University Press 2005-10-10 /pmc/articles/PMC2171229/ /pubmed/16216925 http://dx.doi.org/10.1083/jcb.200507075 Text en Copyright © 2005, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Liao, Maofu
Kielian, Margaret
Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
title Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
title_full Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
title_fullStr Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
title_full_unstemmed Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
title_short Domain III from class II fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
title_sort domain iii from class ii fusion proteins functions as a dominant-negative inhibitor of virus membrane fusion
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2171229/
https://www.ncbi.nlm.nih.gov/pubmed/16216925
http://dx.doi.org/10.1083/jcb.200507075
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