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Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme.

<div class='caption-title'>Structural and functional overview of SARS-CoV-2 nsp10-nsp14-RNA complexes.</div>
<div class='caption-title'>Active-site conformation and catalytic mechanism of SARS-CoV-2 ExoN.</div>
<div class='caption-title'>Mechanism of substrate recognition by SARS-CoV-2 ExoN.</div>
Liu C, Shi W, Becker ST, Schatz DG, Liu B, Yang Y
OpenAccess logo Science 373 1142-1146 (2021)
Related entries: 7n0b, 7n0c

Cited: 61 times
EuropePMC logo PMID: 34315827

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.

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Articles - 7n0d mentioned but not cited (3)

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