7N0D

Cryo-EM structure of the tetrameric form of SARS-CoV-2 nsp10-nsp14 (E191A)-RNA complex

Summary for 7N0D

• Entry DOI: 10.2210/pdb7n0d/pdb
• EMDB information: 24104
• Descriptor: Non-structural protein 10, Proofreading exoribonuclease, RNA (5'-R(*GP*GP*GP*GP*AP*UP*GP*UP*GP*AP*UP*UP*UP*UP*AP*AP*UP*AP*G)-3'), ... (9 entities in total)
• Functional Keywords: sars-cov-2, exoribonuclease, mismatch correction, viral protein-rna complex, viral protein/rna
• Biological source: Severe acute respiratory syndrome coronavirus 2 (2019-nCoV, SARS-CoV-2); More
• Total number of polymer chains: 14
• Total formula weight: 335491.81

Authors

Liu, C.,Yang, Y. (deposition date: 2021-05-25, release date: 2021-07-28, Last modification date: 2025-05-28)

Primary citation

Liu, C.,Shi, W.,Becker, S.T.,Schatz, D.G.,Liu, B.,Yang, Y.
Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.
Science, 373:1142-1146, 2021

PubMed Abstract: Coronavirus 3′-to-5′ exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10–nsp14 complex, boosts replication fidelity by proofreading RNA synthesis and is critical for the virus life cycle. ExoN also recognizes and excises nucleotide analog inhibitors incorporated into the nascent RNA, undermining the effectiveness of nucleotide analog–based antivirals. Here we present cryo–electron microscopy structures of both wild-type and mutant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nsp10-nsp14 in complex with an RNA substrate bearing a 3′-end mismatch at resolutions ranging from 2.5 to 3.9 angstroms. The structures reveal the molecular determinants of ExoN substrate specificity and offer insight into the molecular mechanisms of mismatch correction during coronavirus RNA synthesis. Our findings provide guidance for rational design of improved anticoronavirus therapies.

PubMed: 34315827
DOI: 10.1126/science.abi9310

Experimental method

ELECTRON MICROSCOPY (2.5 Å)