8XCH

SARS-CoV-2 Replication-Transcription Complex has a dimer-of-dimeric architecture (ddRTC) in pre-capping initiation.

8XCH の概要

• エントリーDOI: 10.2210/pdb8xch/pdb
• EMDBエントリー: 38243
• 分子名称: Replicase polyprotein 1ab, PHOSPHATE ION, Non-structural protein 8, ... (10 entities in total)
• 機能のキーワード: sars-cov-2, replication-transcription complex, helicase, rna unwinding, cryo-em, viral protein
• 由来する生物種: Severe acute respiratory syndrome coronavirus 2; 詳細
• タンパク質・核酸の鎖数: 32
• 化学式量合計: 1283424.40

構造登録者

Yan, L.,Lou, Z. (登録日: 2023-12-09, 公開日: 2025-06-11, 最終更新日: 2025-11-12)

主引用文献

Yan, L.,Huang, Y.,Liu, Y.,Ge, J.,Gao, S.,Tan, L.,Liu, L.,Liu, Z.,Ye, S.,Wang, J.,Xiong, J.,Zhou, Y.,Zhao, H.,Zhao, X.,Guddat, L.W.,Gao, Y.,Zhu, L.,Rao, Z.,Lou, Z.
Structural basis for the concurrence of template recycling and RNA capping in SARS-CoV-2.
Cell, 2025

PubMed Abstract: 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.

PubMed: 41130208
DOI: 10.1016/j.cell.2025.09.022

実験手法

ELECTRON MICROSCOPY (3.4 Å)