近日，清华大学娄志勇、饶子和等研究人员合作揭示SARS-CoV-2复制和转录复合体冷冻电镜结构。该项研究成果于2020年11月14日在线发表在《细胞》杂志上。

Title: Cryo-EM structure of an extended SARS-CoV-2 replication and transcription complex reveals an intermediate state in cap synthesis

Author: Liming Yan, Ji Ge, Litao Zheng, Ying Zhang, Yan Gao, Tao Wang, Yucen Huang, Yunxiang Yang, Shan Gao, Mingyu Li, Zhenyu Liu, Haofeng Wang, Yingjian Li, Yu Chen, Luke W. Guddat, Quan Wang, Zihe Rao, Zhiyong Lou

Issue&Volume: 2020-11-14

Abstract: Transcription of SARS-CoV-2 mRNA requires sequential reactions facilitated by the replication and transcription complex (RTC). Here, we present a structural snapshot of SARS-CoV-2 RTC as it transition towards cap structure synthesis. We determine the atomic cryo-EM structure of an extended RTC assembled by nsp7-nsp82-nsp12-nsp132-RNA and a single RNA binding protein nsp9. Nsp9 binds tightly to nsp12 (RdRp) NiRAN, allowing nsp9 N-terminus inserting into the catalytic center of nsp12 NiRAN, which then inhibits activity. We also show that nsp12 NiRAN possesses guanylyltransferase activity, catalyzing the formation of cap core structure (GpppA). The orientation of nsp13 that anchors the 5’ extension of template RNA shows a remarkable conformational shift, resulting in zinc finger 3 of its ZBD inserting into a minor groove of paired template-primer RNA. These results reason an intermediate state of RTC towards mRNA synthesis, pave a way to understand the RTC architecture, and provide a target for antiviral development.

DOI: 10.1016/j.cell.2020.11.016

Source: https://www.cell.com/cell/fulltext/S0092-8674(20)31533-6