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-Structure paper
タイトル | The mechanism of RNA capping by SARS-CoV-2. |
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ジャーナル・号・ページ | Nature, Vol. 609, Issue 7928, Page 793-800, Year 2022 |
掲載日 | 2022年8月9日 |
![]() | Gina J Park / Adam Osinski / Genaro Hernandez / Jennifer L Eitson / Abir Majumdar / Marco Tonelli / Katie Henzler-Wildman / Krzysztof Pawłowski / Zhe Chen / Yang Li / John W Schoggins / Vincent S Tagliabracci / ![]() ![]() ![]() |
PubMed 要旨 | The RNA genome of SARS-CoV-2 contains a 5' cap that facilitates the translation of viral proteins, protection from exonucleases and evasion of the host immune response. How this cap is made in SARS- ...The RNA genome of SARS-CoV-2 contains a 5' cap that facilitates the translation of viral proteins, protection from exonucleases and evasion of the host immune response. How this cap is made in SARS-CoV-2 is not completely understood. Here we reconstitute the N7- and 2'-O-methylated SARS-CoV-2 RNA cap (GpppA) using virally encoded non-structural proteins (nsps). We show that the kinase-like nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain of nsp12 transfers the RNA to the amino terminus of nsp9, forming a covalent RNA-protein intermediate (a process termed RNAylation). Subsequently, the NiRAN domain transfers the RNA to GDP, forming the core cap structure GpppA-RNA. The nsp14 and nsp16 methyltransferases then add methyl groups to form functional cap structures. Structural analyses of the replication-transcription complex bound to nsp9 identified key interactions that mediate the capping reaction. Furthermore, we demonstrate in a reverse genetics system that the N terminus of nsp9 and the kinase-like active-site residues in the NiRAN domain are required for successful SARS-CoV-2 replication. Collectively, our results reveal an unconventional mechanism by which SARS-CoV-2 caps its RNA genome, thus exposing a new target in the development of antivirals to treat COVID-19. |
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手法 | EM (単粒子) |
解像度 | 3.18 Å |
構造データ | EMDB-25898, PDB-7thm: |
化合物 | ![]() ChemComp-ZN: ![]() ChemComp-MN: ![]() ChemComp-POP: |
由来 |
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![]() | VIRAL PROTEIN / polymerase / NiRAN / capping / nsp9 |