9IMK

SARS-CoV-2 Replication-Transcription Complex has a dimer architecture (dRTC) in post-capping state

Summary for 9IMK

• Entry DOI: 10.2210/pdb9imk/pdb
• EMDB information: 60692
• Descriptor: RNA-directed RNA polymerase nsp12, Non-structural protein 8, Non-structural protein 7, ... (9 entities in total)
• Functional Keywords: sars-cov-2, replication-transcription complex, unwinding, rna capping, cryo-em, viral protein/rna, viral protein-rna complex
• Biological source: Severe acute respiratory syndrome coronavirus 2; More
• Total number of polymer chains: 18
• Total formula weight: 676866.45

Authors

Yan, L.M.,Rao, Z.H.,Lou, Z.Y. (deposition date: 2024-07-03, release date: 2025-08-20, Last modification date: 2025-12-24)

Primary citation

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, 188:7194-7205.e10, 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

Experimental method

ELECTRON MICROSCOPY (4.01 Å)