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Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data

The nucleocapsid protein of the SARS-CoV-2 virus comprises two RNA-binding domains and three regions that are intrinsically disordered. While the structures of the RNA-binding domains have been solved using protein crystallography and NMR, current knowledge of the conformations of the full-length nu...

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Autores principales: Różycki, Bartosz, Boura, Evzen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier B.V. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172258/
https://www.ncbi.nlm.nih.gov/pubmed/35696898
http://dx.doi.org/10.1016/j.bpc.2022.106843
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author Różycki, Bartosz
Boura, Evzen
author_facet Różycki, Bartosz
Boura, Evzen
author_sort Różycki, Bartosz
collection PubMed
description The nucleocapsid protein of the SARS-CoV-2 virus comprises two RNA-binding domains and three regions that are intrinsically disordered. While the structures of the RNA-binding domains have been solved using protein crystallography and NMR, current knowledge of the conformations of the full-length nucleocapsid protein is rather limited. To fill in this knowledge gap, we combined coarse-grained molecular simulations with data from small-angle X-ray scattering (SAXS) experiments using the ensemble refinement of SAXS (EROS) method. Our results show that the dimer of the full-length nucleocapsid protein exhibits large conformational fluctuations with its radius of gyration ranging from about 4 to 8 nm. The RNA-binding domains do not make direct contacts. The disordered region that links these two domains comprises a hydrophobic α-helix which makes frequent and nonspecific contacts with the RNA-binding domains. Each of the intrinsically disordered regions adopts conformations that are locally compact, yet on average, much more extended than Gaussian chains of equivalent lengths. We offer a detailed picture of the conformational ensemble of the nucleocapsid protein dimer under near-physiological conditions, which will be important for understanding the nucleocapsid assembly process.
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spelling pubmed-91722582022-06-08 Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data Różycki, Bartosz Boura, Evzen Biophys Chem Article The nucleocapsid protein of the SARS-CoV-2 virus comprises two RNA-binding domains and three regions that are intrinsically disordered. While the structures of the RNA-binding domains have been solved using protein crystallography and NMR, current knowledge of the conformations of the full-length nucleocapsid protein is rather limited. To fill in this knowledge gap, we combined coarse-grained molecular simulations with data from small-angle X-ray scattering (SAXS) experiments using the ensemble refinement of SAXS (EROS) method. Our results show that the dimer of the full-length nucleocapsid protein exhibits large conformational fluctuations with its radius of gyration ranging from about 4 to 8 nm. The RNA-binding domains do not make direct contacts. The disordered region that links these two domains comprises a hydrophobic α-helix which makes frequent and nonspecific contacts with the RNA-binding domains. Each of the intrinsically disordered regions adopts conformations that are locally compact, yet on average, much more extended than Gaussian chains of equivalent lengths. We offer a detailed picture of the conformational ensemble of the nucleocapsid protein dimer under near-physiological conditions, which will be important for understanding the nucleocapsid assembly process. Elsevier B.V. 2022-09 2022-06-07 /pmc/articles/PMC9172258/ /pubmed/35696898 http://dx.doi.org/10.1016/j.bpc.2022.106843 Text en © 2022 Elsevier B.V. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Różycki, Bartosz
Boura, Evzen
Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data
title Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data
title_full Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data
title_fullStr Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data
title_full_unstemmed Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data
title_short Conformational ensemble of the full-length SARS-CoV-2 nucleocapsid (N) protein based on molecular simulations and SAXS data
title_sort conformational ensemble of the full-length sars-cov-2 nucleocapsid (n) protein based on molecular simulations and saxs data
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172258/
https://www.ncbi.nlm.nih.gov/pubmed/35696898
http://dx.doi.org/10.1016/j.bpc.2022.106843
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