SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle
Uložené v:
| Názov: | SARS-CoV-2 nsp3 and nsp4 are minimal constituents of a pore spanning replication organelle |
|---|---|
| Autori: | Zimmermann, Liv, Zhao, Xiaohan, Makroczyova, Jana, Wachsmuth-Melm, Moritz, Prasad, Vibhu, Hensel, Zach, Bartenschlager, Ralf, Chlanda, Petr |
| Zdroj: | Nat Commun Nature Communications, Vol 14, Iss 1, Pp 1-12 (2023) |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2023. |
| Rok vydania: | 2023 |
| Predmety: | Organelles / metabolism, Organelles, SARS-CoV-2, Science, Viral Nonstructural Proteins / genetics, COVID-19, Viral Nonstructural Proteins, Virus Replication, Article, 3. Good health, Humans, SARS-CoV-2 / metabolism, Viral Nonstructural Proteins / metabolism |
| Popis: | Coronavirus replication is associated with the remodeling of cellular membranes, resulting in the formation of double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, the exact components and the structure of the SARS-CoV-2 DMV pore remain to be determined. Here, we investigate the structure of the DMV pore by in situ cryo-electron tomography combined with subtomogram averaging. We identify non-structural protein (nsp) 3 and 4 as minimal components required for the formation of a DMV-spanning pore, which is dependent on nsp3-4 proteolytic cleavage. In addition, we show that Mac2-Mac3-DPUP-Ubl2 domains are critical for nsp3 oligomerization and crown integrity which influences membrane curvature required for biogenesis of DMVs. Altogether, SARS-CoV-2 nsp3-4 have a dual role by driving the biogenesis of replication organelles and assembly of DMV-spanning pores which we propose here to term replicopores. |
| Druh dokumentu: | Article Other literature type |
| Popis súboru: | application/pdf |
| Jazyk: | English |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-023-43666-5 |
| Prístupová URL adresa: | https://pubmed.ncbi.nlm.nih.gov/38036567 https://doaj.org/article/ec898bd6b18840459e8a9139b107c87a https://archive-ouverte.unige.ch/unige:181546 https://doi.org/10.1038/s41467-023-43666-5 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Prístupové číslo: | edsair.doi.dedup.....fb5db74490ec07ed25aa8e8b2d71bc00 |
| Databáza: | OpenAIRE |
Full Text 
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Coronavirus replication is associated with the remodeling of cellular membranes, resulting in the formation of double-membrane vesicles (DMVs). A DMV-spanning pore was identified as a putative portal for viral RNA. However, the exact components and the structure of the SARS-CoV-2 DMV pore remain to be determined. Here, we investigate the structure of the DMV pore by in situ cryo-electron tomography combined with subtomogram averaging. We identify non-structural protein (nsp) 3 and 4 as minimal components required for the formation of a DMV-spanning pore, which is dependent on nsp3-4 proteolytic cleavage. In addition, we show that Mac2-Mac3-DPUP-Ubl2 domains are critical for nsp3 oligomerization and crown integrity which influences membrane curvature required for biogenesis of DMVs. Altogether, SARS-CoV-2 nsp3-4 have a dual role by driving the biogenesis of replication organelles and assembly of DMV-spanning pores which we propose here to term replicopores. |
|---|---|
| ISSN: | 20411723 |
| DOI: | 10.1038/s41467-023-43666-5 |