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Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer
The viral cycle of SARS-CoV-2 is based on a complex interplay with the cellular machinery, which is mediated by specific proteins eluding or hijacking the cellular defense mechanisms. Among the complex pathways induced by the viral infection, autophagy is particularly crucial and is strongly influen...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society of Chemistry
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132136/ https://www.ncbi.nlm.nih.gov/pubmed/35685814 http://dx.doi.org/10.1039/d2sc00108j |
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author | Bignon, Emmanuelle Marazzi, Marco Grandemange, Stéphanie Monari, Antonio |
author_facet | Bignon, Emmanuelle Marazzi, Marco Grandemange, Stéphanie Monari, Antonio |
author_sort | Bignon, Emmanuelle |
collection | PubMed |
description | The viral cycle of SARS-CoV-2 is based on a complex interplay with the cellular machinery, which is mediated by specific proteins eluding or hijacking the cellular defense mechanisms. Among the complex pathways induced by the viral infection, autophagy is particularly crucial and is strongly influenced by the action of the non-structural protein 6 (Nsp6) interacting with the endoplasmic reticulum membrane. Importantly, differently from other non-structural proteins, Nsp6 is mutated in the recently emerged Omicron variant, suggesting a possible different role of autophagy. In this contribution we explore, for the first time, the structural properties of Nsp6 thanks to long-timescale molecular dynamics simulations and machine learning analysis, identifying the interaction patterns with the lipid membrane. We also show how the mutation brought by the Omicron variant may indeed modify some of the specific interactions, and more particularly help anchor the viral protein to the lipid bilayer interface. |
format | Online Article Text |
id | pubmed-9132136 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society of Chemistry |
record_format | MEDLINE/PubMed |
spelling | pubmed-91321362022-06-08 Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer Bignon, Emmanuelle Marazzi, Marco Grandemange, Stéphanie Monari, Antonio Chem Sci Chemistry The viral cycle of SARS-CoV-2 is based on a complex interplay with the cellular machinery, which is mediated by specific proteins eluding or hijacking the cellular defense mechanisms. Among the complex pathways induced by the viral infection, autophagy is particularly crucial and is strongly influenced by the action of the non-structural protein 6 (Nsp6) interacting with the endoplasmic reticulum membrane. Importantly, differently from other non-structural proteins, Nsp6 is mutated in the recently emerged Omicron variant, suggesting a possible different role of autophagy. In this contribution we explore, for the first time, the structural properties of Nsp6 thanks to long-timescale molecular dynamics simulations and machine learning analysis, identifying the interaction patterns with the lipid membrane. We also show how the mutation brought by the Omicron variant may indeed modify some of the specific interactions, and more particularly help anchor the viral protein to the lipid bilayer interface. The Royal Society of Chemistry 2022-05-02 /pmc/articles/PMC9132136/ /pubmed/35685814 http://dx.doi.org/10.1039/d2sc00108j Text en This journal is © The Royal Society of Chemistry https://creativecommons.org/licenses/by/3.0/ |
spellingShingle | Chemistry Bignon, Emmanuelle Marazzi, Marco Grandemange, Stéphanie Monari, Antonio Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer |
title | Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer |
title_full | Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer |
title_fullStr | Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer |
title_full_unstemmed | Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer |
title_short | Autophagy and evasion of the immune system by SARS-CoV-2. Structural features of the non-structural protein 6 from wild type and Omicron viral strains interacting with a model lipid bilayer |
title_sort | autophagy and evasion of the immune system by sars-cov-2. structural features of the non-structural protein 6 from wild type and omicron viral strains interacting with a model lipid bilayer |
topic | Chemistry |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9132136/ https://www.ncbi.nlm.nih.gov/pubmed/35685814 http://dx.doi.org/10.1039/d2sc00108j |
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