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Molecular architecture of the Chikungunya virus replication complex
To better understand how positive-strand (+) RNA viruses assemble membrane-associated replication complexes (RCs) to synthesize, process, and transport viral RNA in virus-infected cells, we determined both the high-resolution structure of the core RNA replicase of chikungunya virus and the native RC...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710867/ https://www.ncbi.nlm.nih.gov/pubmed/36449616 http://dx.doi.org/10.1126/sciadv.add2536 |
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author | Tan, Yaw Bia Chmielewski, David Law, Michelle Cheok Yien Zhang, Kuo He, Yu Chen, Muyuan Jin, Jing Luo, Dahai |
author_facet | Tan, Yaw Bia Chmielewski, David Law, Michelle Cheok Yien Zhang, Kuo He, Yu Chen, Muyuan Jin, Jing Luo, Dahai |
author_sort | Tan, Yaw Bia |
collection | PubMed |
description | To better understand how positive-strand (+) RNA viruses assemble membrane-associated replication complexes (RCs) to synthesize, process, and transport viral RNA in virus-infected cells, we determined both the high-resolution structure of the core RNA replicase of chikungunya virus and the native RC architecture in its cellular context at subnanometer resolution, using in vitro reconstitution and in situ electron cryotomography, respectively. Within the core RNA replicase, the viral polymerase nsP4, which is in complex with nsP2 helicase-protease, sits in the central pore of the membrane-anchored nsP1 RNA-capping ring. The addition of a large cytoplasmic ring next to the C terminus of nsP1 forms the holo-RNA-RC as observed at the neck of spherules formed in virus-infected cells. These results represent a major conceptual advance in elucidating the molecular mechanisms of RNA virus replication and the principles underlying the molecular architecture of RCs, likely to be shared with many pathogenic (+) RNA viruses. |
format | Online Article Text |
id | pubmed-9710867 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-97108672022-12-07 Molecular architecture of the Chikungunya virus replication complex Tan, Yaw Bia Chmielewski, David Law, Michelle Cheok Yien Zhang, Kuo He, Yu Chen, Muyuan Jin, Jing Luo, Dahai Sci Adv Biomedicine and Life Sciences To better understand how positive-strand (+) RNA viruses assemble membrane-associated replication complexes (RCs) to synthesize, process, and transport viral RNA in virus-infected cells, we determined both the high-resolution structure of the core RNA replicase of chikungunya virus and the native RC architecture in its cellular context at subnanometer resolution, using in vitro reconstitution and in situ electron cryotomography, respectively. Within the core RNA replicase, the viral polymerase nsP4, which is in complex with nsP2 helicase-protease, sits in the central pore of the membrane-anchored nsP1 RNA-capping ring. The addition of a large cytoplasmic ring next to the C terminus of nsP1 forms the holo-RNA-RC as observed at the neck of spherules formed in virus-infected cells. These results represent a major conceptual advance in elucidating the molecular mechanisms of RNA virus replication and the principles underlying the molecular architecture of RCs, likely to be shared with many pathogenic (+) RNA viruses. American Association for the Advancement of Science 2022-11-30 /pmc/articles/PMC9710867/ /pubmed/36449616 http://dx.doi.org/10.1126/sciadv.add2536 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Tan, Yaw Bia Chmielewski, David Law, Michelle Cheok Yien Zhang, Kuo He, Yu Chen, Muyuan Jin, Jing Luo, Dahai Molecular architecture of the Chikungunya virus replication complex |
title | Molecular architecture of the Chikungunya virus replication complex |
title_full | Molecular architecture of the Chikungunya virus replication complex |
title_fullStr | Molecular architecture of the Chikungunya virus replication complex |
title_full_unstemmed | Molecular architecture of the Chikungunya virus replication complex |
title_short | Molecular architecture of the Chikungunya virus replication complex |
title_sort | molecular architecture of the chikungunya virus replication complex |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710867/ https://www.ncbi.nlm.nih.gov/pubmed/36449616 http://dx.doi.org/10.1126/sciadv.add2536 |
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