ArticleJournal of virology2005
A complex zinc finger controls the enzymatic activities of nidovirus helicases.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 123 citations in OpenAlex.
- Recent advances in functional studies of coronavirus NSP13 helicase and challenges in inhibitor development.Virulence · 2026Review
- Repurposing drug screen for the identification of helicase inhibitors from viruses of pandemic concern.SLAS discovery : advancing life sciences R & D · 2026Article
- Equine arteritis virus Nsp10 promotes MAVS proteasomal degradation via E3 ligases Smurf1/MARCH5.Journal of virology · 2026Article
- Bat RNA viruses employ viral RHIMs orchestrating species-specific cell death programs linked to Z-RNA sensing and ZBP1-RIPK3 signaling.iScience · 2024Article
- Activity and inhibition of the SARS-CoV-2 Omicron nsp13 R392C variant using RNA duplex unwinding assays.SLAS discovery : advancing life sciences R & D · 2024Article
- Research Progress on the NSP10 Protein of Porcine Reproductive and Respiratory Syndrome Virus.Microorganisms · 2024Review
- Observing inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution.Nucleic acids research · 2023Article
- An iron-sulfur cluster in the zinc-binding domain of the SARS-CoV-2 helicase modulates its RNA-binding and -unwinding activities.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Classification, replication, and transcription ofFrontiers in microbiology · 2023Review
- Inhibition of the SARS-CoV-2 helicase at single-nucleotide resolution.bioRxiv : the preprint server for biology · 2022Article
- Replication of the coronavirus genome: A paradox among positive-strand RNA viruses.The Journal of biological chemistry · 2022Review
- The stalk domain of SARS-CoV-2 NSP13 is essential for its helicase activity.Biochemical and biophysical research communications · 2022Article
- Host and Viral Zinc-Finger Proteins in COVID-19.International journal of molecular sciences · 2022Review
- Conserved Targets to Prevent Emerging Coronaviruses.Viruses · 2022Review
- Ensemble cryo-EM reveals conformational states of the nsp13 helicase in the SARS-CoV-2 helicase replication-transcription complex.Nature structural & molecular biology · 2022Article
- Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design.Nature reviews. Molecular cell biology · 2022Review
- Structure-function analysis of the nsp14 N7-guanine methyltransferase reveals an essential role inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Destruction mechanisms of ozone over SARS-CoV-2.Scientific reports · 2021Article
- Structure, mechanism and crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase.Nature communications · 2021Article
- Identification of an Intramolecular Switch That Controls the Interaction of Helicase nsp10 with Membrane-Associated nsp12 of Porcine Reproductive and Respiratory Syndrome Virus.Journal of virology · 2021Article
25 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Nidoviruses (Coronaviridae, Arteriviridae, and Roniviridae) encode a nonstructural protein, called nsp10 in arteriviruses and nsp13 in coronaviruses, that is comprised of a C-terminal superfamily 1 helicase domain and an N-terminal, putative zinc-binding domain (ZBD). Previously, mutations in the equine arteritis virus (EAV) nsp10 ZBD were shown to block arterivirus reproduction by disrupting RNA synthesis and possibly virion biogenesis. Here, we characterized the ATPase and helicase activities of bacterially expressed mutant forms of nsp10 and its human coronavirus 229E ortholog, nsp13, and correlated these in vitro activities with specific virus phenotypes. Replacement of conserved Cys or His residues with Ala proved to be more deleterious than Cys-for-His or His-for-Cys replacements. Furthermore, denaturation-renaturation experiments revealed that, during protein refolding, Zn2+ is essential for the rescue of the enzymatic activities of nidovirus helicases. Taken together, the data strongly support the zinc-binding function of the N-terminal domain of nidovirus helicases. nsp10 ATPase/helicase deficiency resulting from single-residue substitutions in the ZBD or deletion of the entire domain could not be complemented in trans by wild-type ZBD, suggesting a critical function of the ZBD in cis. Consistently, no viral RNA synthesis was detected after transfection of EAV full-length RNAs encoding ATPase/helicase-deficient nsp10 into susceptible cells. In contrast, diverse phenotypes were observed for mutants with enzymatically active nsp10, which in a number of cases correlated with the activities measured in vitro. Collectively, our data suggest that the ZBD is critically involved in nidovirus replication and transcription by modulating the enzymatic activities of the helicase domain and other, yet unknown, mechanisms.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.