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-Structure paper
タイトル | Structural and functional insights into the enzymatic plasticity of the SARS-CoV-2 NiRAN domain. |
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ジャーナル・号・ページ | Mol Cell, Vol. 83, Issue 21, Page 3921-33930.e7, Year 2023 |
掲載日 | 2023年11月2日 |
著者 | Gabriel I Small / Olga Fedorova / Paul Dominic B Olinares / Joshua Chandanani / Anoosha Banerjee / Young Joo Choi / Henrik Molina / Brian T Chait / Seth A Darst / Elizabeth A Campbell / |
PubMed 要旨 | The enzymatic activity of the SARS-CoV-2 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with ...The enzymatic activity of the SARS-CoV-2 nidovirus RdRp-associated nucleotidyltransferase (NiRAN) domain is essential for viral propagation, with three distinct activities associated with modification of the nsp9 N terminus, NMPylation, RNAylation, and deRNAylation/capping via a GDP-polyribonucleotidyltransferase reaction. The latter two activities comprise an unconventional mechanism for initiating viral RNA 5' cap formation, while the role of NMPylation is unclear. The structural mechanisms for these diverse enzymatic activities have not been properly delineated. Here, we determine high-resolution cryoelectron microscopy (cryo-EM) structures of catalytic intermediates for the NMPylation and deRNAylation/capping reactions, revealing diverse nucleotide binding poses and divalent metal ion coordination sites to promote its repertoire of activities. The deRNAylation/capping structure explains why GDP is a preferred substrate for the capping reaction over GTP. Altogether, these findings enhance our understanding of the promiscuous coronaviral NiRAN domain, a therapeutic target, and provide an accurate structural platform for drug development. |
リンク | Mol Cell / PubMed:37890482 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.9 - 3.06 Å |
構造データ | EMDB-40699, PDB-8sq9: EMDB-40707, PDB-8sqj: EMDB-40708, PDB-8sqk: |
化合物 | ChemComp-ZN: ChemComp-MG: ChemComp-WSB: ChemComp-HOH: ChemComp-VSN: |
由来 |
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キーワード | VIRAL PROTEIN / RTC / nsp12 / nsp9 / NiRAN / SARS-CoV-2 / NMPylation / UMPCPP / deRNAylation / mRNA capping |