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The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions
The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally “closed” State 1 to more “open” conformations, but the molecular mechanisms underl...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648922/ https://www.ncbi.nlm.nih.gov/pubmed/29051495 http://dx.doi.org/10.1038/s41467-017-01119-w |
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author | Herschhorn, Alon Gu, Christopher Moraca, Francesca Ma, Xiaochu Farrell, Mark Smith, Amos B. Pancera, Marie Kwong, Peter D. Schön, Arne Freire, Ernesto Abrams, Cameron Blanchard, Scott C. Mothes, Walther Sodroski, Joseph G. |
author_facet | Herschhorn, Alon Gu, Christopher Moraca, Francesca Ma, Xiaochu Farrell, Mark Smith, Amos B. Pancera, Marie Kwong, Peter D. Schön, Arne Freire, Ernesto Abrams, Cameron Blanchard, Scott C. Mothes, Walther Sodroski, Joseph G. |
author_sort | Herschhorn, Alon |
collection | PubMed |
description | The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally “closed” State 1 to more “open” conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20–β21 element as a major regulator of Env transitions. Several amino acid changes in the β20–β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry. |
format | Online Article Text |
id | pubmed-5648922 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-56489222017-10-23 The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions Herschhorn, Alon Gu, Christopher Moraca, Francesca Ma, Xiaochu Farrell, Mark Smith, Amos B. Pancera, Marie Kwong, Peter D. Schön, Arne Freire, Ernesto Abrams, Cameron Blanchard, Scott C. Mothes, Walther Sodroski, Joseph G. Nat Commun Article The entry of HIV-1 into target cells is mediated by the viral envelope glycoproteins (Env). Binding to the CD4 receptor triggers a cascade of conformational changes in distant domains that move Env from a functionally “closed” State 1 to more “open” conformations, but the molecular mechanisms underlying allosteric regulation of these transitions are still elusive. Here, we develop chemical probes that block CD4-induced conformational changes in Env and use them to identify a potential control switch for Env structural rearrangements. We identify the gp120 β20–β21 element as a major regulator of Env transitions. Several amino acid changes in the β20–β21 base lead to open Env conformations, recapitulating the structural changes induced by CD4 binding. These HIV-1 mutants require less CD4 to infect cells and are relatively resistant to State 1-preferring broadly neutralizing antibodies. These data provide insights into the molecular mechanism and vulnerability of HIV-1 entry. Nature Publishing Group UK 2017-10-19 /pmc/articles/PMC5648922/ /pubmed/29051495 http://dx.doi.org/10.1038/s41467-017-01119-w Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Herschhorn, Alon Gu, Christopher Moraca, Francesca Ma, Xiaochu Farrell, Mark Smith, Amos B. Pancera, Marie Kwong, Peter D. Schön, Arne Freire, Ernesto Abrams, Cameron Blanchard, Scott C. Mothes, Walther Sodroski, Joseph G. The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions |
title | The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions |
title_full | The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions |
title_fullStr | The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions |
title_full_unstemmed | The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions |
title_short | The β20–β21 of gp120 is a regulatory switch for HIV-1 Env conformational transitions |
title_sort | β20–β21 of gp120 is a regulatory switch for hiv-1 env conformational transitions |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5648922/ https://www.ncbi.nlm.nih.gov/pubmed/29051495 http://dx.doi.org/10.1038/s41467-017-01119-w |
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