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

doi:10.1038/s41467-020-19770-1

	Architecture of a SARS-CoV-2 mini replication and transcription complex
	Yan, Liming 1; Zhang, Ying 2; Ge, Ji 2; Zheng, Litao 2; Gao, Yan1,3,4 ; Wang, Tao 1; Jia, Zhihui 5; Wang, Haofeng3,4 ; Huang, Yucen 1; Li, Mingyu 1; Wang, Quan3,4 ; Rao, Zihe1,2,3,4 ; Lou, Zhiyong 1
	2020-11-18
发表期刊	NATURE COMMUNICATIONS
ISSN	2041-1723
卷号	11 期号:1
发表状态	已发表
DOI	10.1038/s41467-020-19770-1
摘要	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. SARS-CoV-2 virus replication and transcription is mediated by the replication and transcription complex (RTC) that is composed of 16 non-structural proteins (nsp). Here, the authors present the cryo-EM structure of a SARS-CoV-2 mini RTC consisting of the viral RNA-dependent RNA polymerase with a template-primer RNA, the RdRp cofactors nsp7 and nsp8 and two nsp13 helicase molecules, and they propose a model for helicase-polymerase coupling during SARS-CoV-2 RTC assembly.
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收录类别	SCI ; SCIE
语种	英语
资助项目	National Program on Key Research Project of China[2020YFA0707500][2017YFC0840300]
WOS研究方向	Science & Technology - Other Topics
WOS类目	Multidisciplinary Sciences
WOS记录号	WOS:000595686500001
出版者	NATURE RESEARCH
引用统计
文献类型	期刊论文
条目标识符	https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/124691
专题	免疫化学研究所_特聘教授组_饶子和组生命科学与技术学院免疫化学研究所_PI研究组_杨海涛组免疫化学研究所_PI研究组_王权组
通讯作者	Rao, Zihe; Lou, Zhiyong
作者单位	1.Tsinghua Univ, Sch Med, MOE Key Lab Prot Sci, Beijing, Peoples R China 2.Tsinghua Univ, Sch Life Sci, Beijing, Peoples R China 3.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China 4.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China 5.Capital Med Univ, Sch Basic Med Sci, Dept Med Microbiol & Parasitol, Res Ctr Microbiome, Beijing, Peoples R China
通讯作者单位	免疫化学研究所; 生命科学与技术学院
推荐引用方式 GB/T 7714	Yan, Liming,Zhang, Ying,Ge, Ji,et al. Architecture of a SARS-CoV-2 mini replication and transcription complex[J]. NATURE COMMUNICATIONS,2020,11(1).
APA	Yan, Liming.,Zhang, Ying.,Ge, Ji.,Zheng, Litao.,Gao, Yan.,...&Lou, Zhiyong.(2020).Architecture of a SARS-CoV-2 mini replication and transcription complex.NATURE COMMUNICATIONS,11(1).
MLA	Yan, Liming,et al."Architecture of a SARS-CoV-2 mini replication and transcription complex".NATURE COMMUNICATIONS 11.1(2020).