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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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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2005
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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. |
format | Text |
id | pubmed-2171229 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2005 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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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