Architecture of a SARS-CoV-2 mini replication and transcription complex

Liming Yan; Ying Zhang; Ji Ge; Litao Zheng; Yan Gao; Tao Wang; Zhihui Jia; Haofeng Wang; Yucen Huang; Mingyu Li; Quan Wang; Zihe Rao; Zhiyong Lou

doi:10.1038/s41467-020-19770-1

Architecture of a SARS-CoV-2 mini replication and transcription complex

Liming Yan, Ying Zhang, Ji Ge, Litao Zheng, Yan Gao, Tao Wang, Zhihui Jia, Haofeng Wang, Yucen Huang, Mingyu Li, Quan Wang, Zihe Rao, Zhiyong Lou

Research output: Contribution to journal › Article › peer-review

150 Citations (Scopus)

Abstract

Non-structural proteins (nsp) constitute the SARS-CoV-2 replication and transcription complex (RTC) to play a pivotal role in the virus life cycle. Here we determine the atomic structure of a SARS-CoV-2 mini RTC, assembled by viral RNA-dependent RNA polymerase (RdRp, nsp12) with a template-primer RNA, nsp7 and nsp8, and two helicase molecules (nsp13-1 and nsp13-2), by cryo-electron microscopy. Two groups of mini RTCs with different conformations of nsp13-1 are identified. In both of them, nsp13-1 stabilizes overall architecture of the mini RTC by contacting with nsp13-2, which anchors the 5′-extension of RNA template, as well as interacting with nsp7-nsp8-nsp12-RNA. Orientation shifts of nsp13-1 results in its variable interactions with other components in two forms of mini RTC. The mutations on nsp13-1:nsp12 and nsp13-1:nsp13-2 interfaces prohibit the enhancement of helicase activity achieved by mini RTCs. These results provide an insight into how helicase couples with polymerase to facilitate its function in virus replication and transcription.

Original language	English
Article number	5874
Journal	Nature Communications
Volume	11
Issue number	1
DOIs	https://doi.org/10.1038/s41467-020-19770-1
Publication status	Published - Dec 2020
Externally published	Yes

Bibliographical note

Funding Information:
We would like to thank the Bio-Electron Microscopy Facility of ShanghaiTech University for the data collection. This work was supported by the National Program on Key Research Project of China (2020YFA0707500 and 2017YFC0840300) and Tsinghua University Spring Breeze Fund.

Publisher Copyright:
© 2020, The Author(s).

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

PubMed: MeSH publication types

Journal Article
Research Support, Non-U.S. Gov't

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10.1038/s41467-020-19770-1

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Yan, L., Zhang, Y., Ge, J., Zheng, L., Gao, Y., Wang, T., Jia, Z., Wang, H., Huang, Y., Li, M., Wang, Q., Rao, Z., & Lou, Z. (2020). Architecture of a SARS-CoV-2 mini replication and transcription complex. Nature Communications, 11(1), Article 5874. https://doi.org/10.1038/s41467-020-19770-1

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AU - Rao, Zihe

AU - Lou, Zhiyong

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Architecture of a SARS-CoV-2 mini replication and transcription complex

Abstract

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