Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.
Science
; 373(6559): 1142-1146, 2021 Sep 03.
Article
in English
| MEDLINE | ID: covidwho-1329031
ABSTRACT
Coronavirus 3'-to-5' exoribonuclease (ExoN), residing in the nonstructural protein (nsp) 10nsp14 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 analogbased antivirals. Here we present cryoelectron 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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Viral Nonstructural Proteins
/
Exoribonucleases
/
DNA Mismatch Repair
/
Viral Regulatory and Accessory Proteins
/
SARS-CoV-2
Limits:
Humans
Language:
English
Journal:
Science
Year:
2021
Document Type:
Article
Affiliation country:
Science.abi9310
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