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Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-...

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Autores principales: Di Matteo, Francesca, Frumenzio, Giorgia, Chandramouli, Balasubramanian, Grottesi, Alessandro, Emerson, Andrew, Musiani, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738952/
https://www.ncbi.nlm.nih.gov/pubmed/36499049
http://dx.doi.org/10.3390/ijms232314721
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author Di Matteo, Francesca
Frumenzio, Giorgia
Chandramouli, Balasubramanian
Grottesi, Alessandro
Emerson, Andrew
Musiani, Francesco
author_facet Di Matteo, Francesca
Frumenzio, Giorgia
Chandramouli, Balasubramanian
Grottesi, Alessandro
Emerson, Andrew
Musiani, Francesco
author_sort Di Matteo, Francesca
collection PubMed
description Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-dependent RNA polymerase together with accessory factors. One of the latter is the protein helicase (NSP13), which is essential for viral replication. The recently solved helicase structure revealed a tertiary structure composed of five domains. Here, we investigated NSP13 from a structural point of view, comparing its RNA-free form with the RNA-engaged form by using atomistic molecular dynamics (MD) simulations at the microsecond timescale. Structural analyses revealed conformational changes that provide insights into the contribution of the different domains, identifying the residues responsible for domain–domain interactions in both observed forms. The RNA-free system appears to be more flexible than the RNA-engaged form. This result underlies the stabilizing role of the nucleic acid and the functional core role of these domains.
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spelling pubmed-97389522022-12-11 Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form Di Matteo, Francesca Frumenzio, Giorgia Chandramouli, Balasubramanian Grottesi, Alessandro Emerson, Andrew Musiani, Francesco Int J Mol Sci Article Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic that broke out in 2020 and continues to be the cause of massive global upheaval. Coronaviruses are positive-strand RNA viruses with a genome of ~30 kb. The genome is replicated and transcribed by RNA-dependent RNA polymerase together with accessory factors. One of the latter is the protein helicase (NSP13), which is essential for viral replication. The recently solved helicase structure revealed a tertiary structure composed of five domains. Here, we investigated NSP13 from a structural point of view, comparing its RNA-free form with the RNA-engaged form by using atomistic molecular dynamics (MD) simulations at the microsecond timescale. Structural analyses revealed conformational changes that provide insights into the contribution of the different domains, identifying the residues responsible for domain–domain interactions in both observed forms. The RNA-free system appears to be more flexible than the RNA-engaged form. This result underlies the stabilizing role of the nucleic acid and the functional core role of these domains. MDPI 2022-11-25 /pmc/articles/PMC9738952/ /pubmed/36499049 http://dx.doi.org/10.3390/ijms232314721 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di Matteo, Francesca
Frumenzio, Giorgia
Chandramouli, Balasubramanian
Grottesi, Alessandro
Emerson, Andrew
Musiani, Francesco
Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
title Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
title_full Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
title_fullStr Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
title_full_unstemmed Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
title_short Computational Study of Helicase from SARS-CoV-2 in RNA-Free and Engaged Form
title_sort computational study of helicase from sars-cov-2 in rna-free and engaged form
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9738952/
https://www.ncbi.nlm.nih.gov/pubmed/36499049
http://dx.doi.org/10.3390/ijms232314721
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