6XEZ

Structure of SARS-CoV-2 replication-transcription complex bound to nsp13 helicase - nsp13(2)-RTC

Summary for 6XEZ

• Entry DOI: 10.2210/pdb6xez/pdb
• EMDB information: 22160 22270 22271
• Descriptor: RNA-directed RNA polymerase, CHAPSO, ALUMINUM FLUORIDE, ... (11 entities in total)
• Functional Keywords: rna-dependent rna polymerase, viral replication-transcription complex, transcription, viral proteins, transferase-hydrolase-rna complex, transferase/hydrolase/rna
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV); More
• Total number of polymer chains: 8
• Total formula weight: 327962.35

Authors

Chen, J.,Malone, B.,Llewellyn, E.C.,Campbell, E.A.,Darst, S.A. (deposition date: 2020-06-14, release date: 2020-07-29, Last modification date: 2025-05-28)

Primary citation

Chen, J.,Malone, B.,Llewellyn, E.,Grasso, M.,Shelton, P.M.M.,Olinares, P.D.B.,Maruthi, K.,Eng, E.T.,Vatandaslar, H.,Chait, B.T.,Kapoor, T.M.,Darst, S.A.,Campbell, E.A.
Structural Basis for Helicase-Polymerase Coupling in the SARS-CoV-2 Replication-Transcription Complex.
Cell, 182:1560-1573.e13, 2020

PubMed Abstract: 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.

PubMed: 32783916
DOI: 10.1016/j.cell.2020.07.033

Experimental method

ELECTRON MICROSCOPY (3.5 Å)