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Structure of SARS-CoV-2 M protein in lipid nanodiscs
SARS-CoV-2 encodes four structural proteins incorporated into virions, spike (S), envelope (E), nucleocapsid (N), and membrane (M). M plays an essential role in viral assembly by organizing other structural proteins through physical interactions and directing them to sites of viral budding. As the m...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9642992/ https://www.ncbi.nlm.nih.gov/pubmed/36264056 http://dx.doi.org/10.7554/eLife.81702 |
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author | Dolan, Kimberly A Dutta, Mandira Kern, David M Kotecha, Abhay Voth, Gregory A Brohawn, Stephen G |
author_facet | Dolan, Kimberly A Dutta, Mandira Kern, David M Kotecha, Abhay Voth, Gregory A Brohawn, Stephen G |
author_sort | Dolan, Kimberly A |
collection | PubMed |
description | SARS-CoV-2 encodes four structural proteins incorporated into virions, spike (S), envelope (E), nucleocapsid (N), and membrane (M). M plays an essential role in viral assembly by organizing other structural proteins through physical interactions and directing them to sites of viral budding. As the most abundant protein in the viral envelope and a target of patient antibodies, M is a compelling target for vaccines and therapeutics. Still, the structure of M and molecular basis for its role in virion formation are unknown. Here, we present the cryo-EM structure of SARS-CoV-2 M in lipid nanodiscs to 3.5 Å resolution. M forms a 50 kDa homodimer that is structurally related to the SARS-CoV-2 ORF3a viroporin, suggesting a shared ancestral origin. Structural comparisons reveal how intersubunit gaps create a small, enclosed pocket in M and large open cavity in ORF3a, consistent with a structural role and ion channel activity, respectively. M displays a strikingly electropositive cytosolic surface that may be important for interactions with N, S, and viral RNA. Molecular dynamics simulations show a high degree of structural rigidity in a simple lipid bilayer and support a role for M homodimers in scaffolding viral assembly. Together, these results provide insight into roles for M in coronavirus assembly and structure. |
format | Online Article Text |
id | pubmed-9642992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-96429922022-11-15 Structure of SARS-CoV-2 M protein in lipid nanodiscs Dolan, Kimberly A Dutta, Mandira Kern, David M Kotecha, Abhay Voth, Gregory A Brohawn, Stephen G eLife Structural Biology and Molecular Biophysics SARS-CoV-2 encodes four structural proteins incorporated into virions, spike (S), envelope (E), nucleocapsid (N), and membrane (M). M plays an essential role in viral assembly by organizing other structural proteins through physical interactions and directing them to sites of viral budding. As the most abundant protein in the viral envelope and a target of patient antibodies, M is a compelling target for vaccines and therapeutics. Still, the structure of M and molecular basis for its role in virion formation are unknown. Here, we present the cryo-EM structure of SARS-CoV-2 M in lipid nanodiscs to 3.5 Å resolution. M forms a 50 kDa homodimer that is structurally related to the SARS-CoV-2 ORF3a viroporin, suggesting a shared ancestral origin. Structural comparisons reveal how intersubunit gaps create a small, enclosed pocket in M and large open cavity in ORF3a, consistent with a structural role and ion channel activity, respectively. M displays a strikingly electropositive cytosolic surface that may be important for interactions with N, S, and viral RNA. Molecular dynamics simulations show a high degree of structural rigidity in a simple lipid bilayer and support a role for M homodimers in scaffolding viral assembly. Together, these results provide insight into roles for M in coronavirus assembly and structure. eLife Sciences Publications, Ltd 2022-10-20 /pmc/articles/PMC9642992/ /pubmed/36264056 http://dx.doi.org/10.7554/eLife.81702 Text en © 2022, Dolan et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Structural Biology and Molecular Biophysics Dolan, Kimberly A Dutta, Mandira Kern, David M Kotecha, Abhay Voth, Gregory A Brohawn, Stephen G Structure of SARS-CoV-2 M protein in lipid nanodiscs |
title | Structure of SARS-CoV-2 M protein in lipid nanodiscs |
title_full | Structure of SARS-CoV-2 M protein in lipid nanodiscs |
title_fullStr | Structure of SARS-CoV-2 M protein in lipid nanodiscs |
title_full_unstemmed | Structure of SARS-CoV-2 M protein in lipid nanodiscs |
title_short | Structure of SARS-CoV-2 M protein in lipid nanodiscs |
title_sort | structure of sars-cov-2 m protein in lipid nanodiscs |
topic | Structural Biology and Molecular Biophysics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9642992/ https://www.ncbi.nlm.nih.gov/pubmed/36264056 http://dx.doi.org/10.7554/eLife.81702 |
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