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Structure paper

TitleStructural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.
Journal, issue, pagesScience, Vol. 373, Issue 6559, Page 1142-1146, Year 2021
Publish dateSep 3, 2021
AuthorsChang Liu / Wei Shi / Scott T Becker / David G Schatz / Bin Liu / Yang Yang /
PubMed AbstractCoronavirus 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 ...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.
External linksScience / PubMed:34315827 / PubMed Central
MethodsEM (single particle)
Resolution2.5 - 3.9 Å
Structure data

24102

7n0b

EMDB-24102, PDB-7n0b:
Cryo-EM structure of SARS-CoV-2 nsp10-nsp14 (WT)-RNA complex
Method: EM (single particle) / Resolution: 3.9 Å

24103

7n0c

EMDB-24103, PDB-7n0c:
Cryo-EM structure of the monomeric form of SARS-CoV-2 nsp10-nsp14 (E191A)-RNA complex
Method: EM (single particle) / Resolution: 3.4 Å

24104

7n0d

EMDB-24104, PDB-7n0d:
Cryo-EM structure of the tetrameric form of SARS-CoV-2 nsp10-nsp14 (E191A)-RNA complex
Method: EM (single particle) / Resolution: 2.5 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-CA:
Unknown entry

ChemComp-HOH:
WATER

ChemComp-MG:
Unknown entry

ChemComp-1N7:
CHAPSO / detergent*YM

Source
  • severe acute respiratory syndrome coronavirus 2
KeywordsVIRAL PROTEIN/RNA / SARS-CoV-2 / exoribonuclease / mismatch correction / VIRAL PROTEIN-RNA complex

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