National Natural Science Foundation of China (NSFC)
中国
引用
ジャーナル: Cell / 年: 2025 タイトル: Structural basis for the concurrence of template recycling and RNA capping in SARS-CoV-2. 著者: Liming Yan / Yucen Huang / Yixiao Liu / Ji Ge / Shan Gao / Liping Tan / Lu Liu / Zhenyu Liu / Sihan Ye / Junbo Wang / Jiangran Xiong / Yu Zhou / Hesheng Zhao / Xiaoyue Zhao / Luke W Guddat / ...著者: Liming Yan / Yucen Huang / Yixiao Liu / Ji Ge / Shan Gao / Liping Tan / Lu Liu / Zhenyu Liu / Sihan Ye / Junbo Wang / Jiangran Xiong / Yu Zhou / Hesheng Zhao / Xiaoyue Zhao / Luke W Guddat / Yan Gao / Lan Zhu / Zihe Rao / Zhiyong Lou / 要旨: In the SARS-CoV-2 replication-transcription complex (RTC), the nascent template-product duplex is unwound into a template strand for recycling and a product strand that needs to be capped. Here, we ...In the SARS-CoV-2 replication-transcription complex (RTC), the nascent template-product duplex is unwound into a template strand for recycling and a product strand that needs to be capped. Here, we determined structures of the SARS-CoV-2 RTC in the pre- and post-capping initiation (CI) states. In the pre-CI state, the RTC has a dimer-of-dimeric architecture (ddRTC). The upstream RNA duplex in one RTC is reciprocally unwound by a helicase in a head-to-head-positioned RTC in the 3'-5' direction. The helicases bind either ADP or ADP⋅P in their ATP-binding pockets, suggesting a mechanism for ATP-hydrolysis-driven unwinding. In the post-CI state, the binding of nsp9 to the nsp12 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) disrupts the ddRTC. The N terminus of nsp9 and the triphosphorylated 5' end of the product strand co-localize in NiRAN's catalytic site, exhibiting the state prior to nsp9 RNAylation for capping. These results provide an insight into the concurrence of template recycling and RNA capping in the SARS-CoV-2 RTC.