National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41 GM103310
米国
Simons Foundation
SF349247
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
U24 GM129539
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41 GM109824
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
P41 GM103314
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM130234
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35 GM118130
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01 GM114450
米国
引用
ジャーナル: Cell / 年: 2020 タイトル: Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Replication-Transcription Complex. 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 ...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 / 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.