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Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface
The hantavirus envelope glycoproteins Gn and Gc mediate virion assembly and cell entry, with Gc driving fusion of viral and endosomal membranes. Although the X-ray structures and overall arrangement of Gn and Gc on the hantavirus spikes are known, their detailed interactions are not. Here we show th...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609335/ https://www.ncbi.nlm.nih.gov/pubmed/31180319 http://dx.doi.org/10.7554/eLife.46028 |
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author | Bignon, Eduardo A Albornoz, Amelina Guardado-Calvo, Pablo Rey, Félix A Tischler, Nicole D |
author_facet | Bignon, Eduardo A Albornoz, Amelina Guardado-Calvo, Pablo Rey, Félix A Tischler, Nicole D |
author_sort | Bignon, Eduardo A |
collection | PubMed |
description | The hantavirus envelope glycoproteins Gn and Gc mediate virion assembly and cell entry, with Gc driving fusion of viral and endosomal membranes. Although the X-ray structures and overall arrangement of Gn and Gc on the hantavirus spikes are known, their detailed interactions are not. Here we show that the lateral contacts between spikes are mediated by the same 2-fold contacts observed in Gc crystals at neutral pH, allowing the engineering of disulfide bonds to cross-link spikes. Disrupting the observed dimer interface affects particle assembly and overall spike stability. We further show that the spikes display a temperature-dependent dynamic behavior at neutral pH, alternating between ‘open’ and ‘closed’ forms. We show that the open form exposes the Gc fusion loops but is off-pathway for productive Gc-induced membrane fusion and cell entry. These data also provide crucial new insights for the design of optimized Gn/Gc immunogens to elicit protective immune responses. |
format | Online Article Text |
id | pubmed-6609335 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-66093352019-07-08 Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface Bignon, Eduardo A Albornoz, Amelina Guardado-Calvo, Pablo Rey, Félix A Tischler, Nicole D eLife Biochemistry and Chemical Biology The hantavirus envelope glycoproteins Gn and Gc mediate virion assembly and cell entry, with Gc driving fusion of viral and endosomal membranes. Although the X-ray structures and overall arrangement of Gn and Gc on the hantavirus spikes are known, their detailed interactions are not. Here we show that the lateral contacts between spikes are mediated by the same 2-fold contacts observed in Gc crystals at neutral pH, allowing the engineering of disulfide bonds to cross-link spikes. Disrupting the observed dimer interface affects particle assembly and overall spike stability. We further show that the spikes display a temperature-dependent dynamic behavior at neutral pH, alternating between ‘open’ and ‘closed’ forms. We show that the open form exposes the Gc fusion loops but is off-pathway for productive Gc-induced membrane fusion and cell entry. These data also provide crucial new insights for the design of optimized Gn/Gc immunogens to elicit protective immune responses. eLife Sciences Publications, Ltd 2019-06-10 /pmc/articles/PMC6609335/ /pubmed/31180319 http://dx.doi.org/10.7554/eLife.46028 Text en © 2019, Bignon et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Biochemistry and Chemical Biology Bignon, Eduardo A Albornoz, Amelina Guardado-Calvo, Pablo Rey, Félix A Tischler, Nicole D Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface |
title | Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface |
title_full | Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface |
title_fullStr | Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface |
title_full_unstemmed | Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface |
title_short | Molecular organization and dynamics of the fusion protein Gc at the hantavirus surface |
title_sort | molecular organization and dynamics of the fusion protein gc at the hantavirus surface |
topic | Biochemistry and Chemical Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6609335/ https://www.ncbi.nlm.nih.gov/pubmed/31180319 http://dx.doi.org/10.7554/eLife.46028 |
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