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-Structure paper
タイトル | Structural basis of mismatch recognition by a SARS-CoV-2 proofreading enzyme. |
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ジャーナル・号・ページ | Science, Vol. 373, Issue 6559, Page 1142-1146, Year 2021 |
掲載日 | 2021年9月3日 |
著者 | Chang Liu / Wei Shi / Scott T Becker / David G Schatz / Bin Liu / Yang Yang / |
PubMed 要旨 | 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 ...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. |
リンク | Science / PubMed:34315827 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.5 - 3.9 Å |
構造データ | EMDB-24102, PDB-7n0b: EMDB-24103, PDB-7n0c: EMDB-24104, PDB-7n0d: |
化合物 | ChemComp-ZN: ChemComp-CA: ChemComp-HOH: ChemComp-MG: ChemComp-1N7: |
由来 |
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キーワード | VIRAL PROTEIN/RNA / SARS-CoV-2 / exoribonuclease / mismatch correction / VIRAL PROTEIN-RNA complex |