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-Structure paper
タイトル | Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Replication-Transcription Complex. |
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ジャーナル・号・ページ | Cell, Vol. 182, Issue 6, Page 1560-1573.e13, Year 2020 |
掲載日 | 2020年9月17日 |
著者 | James Chen / Brandon Malone / Eliza Llewellyn / Michael Grasso / Patrick M M Shelton / Paul Dominic B Olinares / Kashyap Maruthi / Edward T Eng / Hasan Vatandaslar / Brian T Chait / Tarun M Kapoor / Seth A Darst / Elizabeth A Campbell / |
PubMed 要旨 | SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp8/nsp12) along with a ...SARS-CoV-2 is the causative agent of the 2019-2020 pandemic. The SARS-CoV-2 genome is replicated and transcribed by the RNA-dependent RNA polymerase holoenzyme (subunits nsp7/nsp8/nsp12) along with a cast of accessory factors. One of these factors is the nsp13 helicase. Both the holo-RdRp and nsp13 are essential for viral replication and are targets for treating the disease COVID-19. Here we present cryoelectron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template product in complex with two molecules of the nsp13 helicase. The Nidovirales order-specific N-terminal domains of each nsp13 interact with the N-terminal extension of each copy of nsp8. One nsp13 also contacts the nsp12 thumb. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. We also observe ADP-Mg bound in the nsp12 N-terminal nidovirus RdRp-associated nucleotidyltransferase domain, detailing a new pocket for anti-viral therapy development. |
リンク | Cell / PubMed:32783916 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.5 Å |
構造データ | EMDB-22160, PDB-6xez: |
化合物 | ChemComp-ZN: ChemComp-MG: ChemComp-ADP: ChemComp-1N7: ChemComp-AF3: |
由来 |
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キーワード | TRANSFERASE/HYDROLASE/RNA / RNA-dependent RNA polymerase / viral replication-transcription complex / transcription / viral proteins / TRANSFERASE-HYDROLASE-RNA complex |