EMD-30504

Single-particle
2.83 Å
EMD-30504 Deposition: 04/09/2020
Map released: 09/12/2020
Last modified: 27/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links

EMD-30504

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

EMD-30504

Single-particle
2.83 Å
EMD-30504 Deposition: 04/09/2020
Map released: 09/12/2020
Last modified: 27/03/2024
Overview 3D View Sample Experiment Validation Volume Browser Additional data Links
Sample Organism: Severe acute respiratory syndrome coronavirus 2
Sample: SARS-CoV-2 extended RTC
Fitted models: 7cyq (Avg. Q-score: 0.384)

Deposition Authors: Yan L, Ge J
Cryo-EM Structure of an Extended SARS-CoV-2 Replication and Transcription Complex Reveals an Intermediate State in Cap Synthesis.
Yan L, Ge J, Zheng L, Zhang Y, Gao Y, Wang T, Huang Y, Yang Y, Gao S, Li M, Liu Z, Wang H, Li Y, Chen Y, Guddat LW, Wang Q, Rao Z, Lou Z
(2021) Cell , 184 , 184 - 193.e10
PUBMED: 33232691
DOI: doi:10.1016/j.cell.2020.11.016
ISSN: 1097-4172
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 transitions toward 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 toward mRNA synthesis, pave a way to understand the RTC architecture, and provide a target for antiviral development.