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Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope

Envelope glycoproteins from genetically-divergent virus families comprise fusion peptides (FPs) that have been posited to insert and perturb the membranes of target cells upon activation of the virus-cell fusion reaction. Conserved sequences rich in aromatic residues juxtaposed to the external leafl...

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Autores principales: de la Arada, Igor, Torralba, Johana, Tascón, Igor, Colom, Adai, Ubarretxena-Belandia, Iban, Arrondo, José L. R., Apellániz, Beatriz, Nieva, José L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809034/
https://www.ncbi.nlm.nih.gov/pubmed/33446748
http://dx.doi.org/10.1038/s41598-020-80156-w
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author de la Arada, Igor
Torralba, Johana
Tascón, Igor
Colom, Adai
Ubarretxena-Belandia, Iban
Arrondo, José L. R.
Apellániz, Beatriz
Nieva, José L.
author_facet de la Arada, Igor
Torralba, Johana
Tascón, Igor
Colom, Adai
Ubarretxena-Belandia, Iban
Arrondo, José L. R.
Apellániz, Beatriz
Nieva, José L.
author_sort de la Arada, Igor
collection PubMed
description Envelope glycoproteins from genetically-divergent virus families comprise fusion peptides (FPs) that have been posited to insert and perturb the membranes of target cells upon activation of the virus-cell fusion reaction. Conserved sequences rich in aromatic residues juxtaposed to the external leaflet of the virion-wrapping membranes are also frequently found in viral fusion glycoproteins. These membrane-proximal external regions (MPERs) have been implicated in the promotion of the viral membrane restructuring event required for fusion to proceed, hence, proposed to comprise supplementary FPs. However, it remains unknown whether the structure–function relationships governing canonical FPs also operate in the mirroring MPER sequences. Here, we combine infrared spectroscopy-based approaches with cryo-electron microscopy to analyze the alternating conformations adopted, and perturbations generated in membranes by CpreTM, a peptide derived from the MPER of the HIV-1 Env glycoprotein. Altogether, our structural and morphological data support a cholesterol-dependent conformational plasticity for this HIV-1 sequence, which could assist cell-virus fusion by destabilizing the viral membrane at the initial stages of the process.
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spelling pubmed-78090342021-01-15 Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope de la Arada, Igor Torralba, Johana Tascón, Igor Colom, Adai Ubarretxena-Belandia, Iban Arrondo, José L. R. Apellániz, Beatriz Nieva, José L. Sci Rep Article Envelope glycoproteins from genetically-divergent virus families comprise fusion peptides (FPs) that have been posited to insert and perturb the membranes of target cells upon activation of the virus-cell fusion reaction. Conserved sequences rich in aromatic residues juxtaposed to the external leaflet of the virion-wrapping membranes are also frequently found in viral fusion glycoproteins. These membrane-proximal external regions (MPERs) have been implicated in the promotion of the viral membrane restructuring event required for fusion to proceed, hence, proposed to comprise supplementary FPs. However, it remains unknown whether the structure–function relationships governing canonical FPs also operate in the mirroring MPER sequences. Here, we combine infrared spectroscopy-based approaches with cryo-electron microscopy to analyze the alternating conformations adopted, and perturbations generated in membranes by CpreTM, a peptide derived from the MPER of the HIV-1 Env glycoprotein. Altogether, our structural and morphological data support a cholesterol-dependent conformational plasticity for this HIV-1 sequence, which could assist cell-virus fusion by destabilizing the viral membrane at the initial stages of the process. Nature Publishing Group UK 2021-01-14 /pmc/articles/PMC7809034/ /pubmed/33446748 http://dx.doi.org/10.1038/s41598-020-80156-w Text en © The Author(s) 2021 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
de la Arada, Igor
Torralba, Johana
Tascón, Igor
Colom, Adai
Ubarretxena-Belandia, Iban
Arrondo, José L. R.
Apellániz, Beatriz
Nieva, José L.
Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope
title Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope
title_full Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope
title_fullStr Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope
title_full_unstemmed Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope
title_short Conformational plasticity underlies membrane fusion induced by an HIV sequence juxtaposed to the lipid envelope
title_sort conformational plasticity underlies membrane fusion induced by an hiv sequence juxtaposed to the lipid envelope
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809034/
https://www.ncbi.nlm.nih.gov/pubmed/33446748
http://dx.doi.org/10.1038/s41598-020-80156-w
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