ArticleThe Journal of biological chemistry2020
Motif V regulates energy transduction between the flavivirus NS3 ATPase and RNA-binding cleft.
Article in The Journal of biological chemistry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Allosteric Regulation of RNA Affinity by Motif V-VI Coupling in West Nile Virus NS3 Helicase.Proteins · 2026Article
- NS5 polymerase stimulates RNA duplex unwinding by the Orthoflavivirus NS3 helicase.The Journal of biological chemistry · 2026Article
- Motif V is an allosteric couple between the SARS-CoV-2 nsp13 nucleotide triphosphatase and helicase active sites.The Journal of biological chemistry · 2026Article
- Unwinding of an RNA duplex by the Orthoflavivirus NS3 helicase requires translocation beyond the displaced strand and is stimulated by the NS5 RdRp.bioRxiv : the preprint server for biology · 2026Article
- Interaction of West Nile virus NS5 with orthoflavivirus SLA RNAs and their effects on viral replication and inhibition.Journal of virology · 2025Article
- An integrated proteomics approach identifies phosphorylation sites on viral and host proteins that regulate West Nile virus infection.Cell reports · 2025Article
- The Role of SF1 and SF2 Helicases in Biotechnological Applications.Applied biochemistry and biotechnology · 2024Review
- Motif-VI loop acts as a nucleotide valve in the West Nile Virus NS3 Helicase.Nucleic acids research · 2024Article
- Role of ATP Hydrolysis and Product Release in the Translocation Mechanism of SARS-CoV-2 NSP13.The journal of physical chemistry. B · 2024Article
- Deciphering the interaction surface between the West Nile virus NS3 and NS5 proteins.Access microbiology · 2024Article
- Conformational Changes and ATP Hydrolysis in Zika Helicase: The Molecular Basis of a Biomolecular Motor Unveiled by Multiscale Simulations.Journal of the American Chemical Society · 2023Article
- Impact of bound ssRNA length on allostery in the Dengue Virus NS3 helicase.Nucleic acids research · 2023Article
- Article
- Review
- Conserved motifs in the flavivirus NS3 RNA helicase enzyme.Wiley interdisciplinary reviews. RNA · 2022Review
- Dissecting protein domain variability in the core RNA interference machinery of five insect orders.RNA biology · 2021Article
- Structure and function of DEAH-box helicase 32 and its role in cancer.Oncology letters · 2021Review
- A Hyperactive Kunjin Virus NS3 Helicase Mutant Demonstrates Increased Dissemination and Mortality in Mosquitoes.Journal of virology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The unwinding of dsRNA intermediates is critical for the replication of flavivirus RNA genomes. This activity is provided by the C-terminal helicase domain of viral nonstructural protein 3 (NS3). As a member of the superfamily 2 (SF2) helicases, NS3 requires the binding and hydrolysis of ATP/NTP to translocate along and unwind double-stranded nucleic acids. However, the mechanism of energy transduction between the ATP- and RNA-binding pockets is not well-understood. Previous molecular dynamics simulations conducted by our group have identified Motif V as a potential "communication hub" for this energy transduction pathway. To investigate the role of Motif V in this process, here we combined molecular dynamics, biochemistry, and virology approaches. We tested Motif V mutations in both the replicon and recombinant protein systems to investigate viral genome replication, RNA-binding affinity, ATP hydrolysis activity, and helicase-mediated unwinding activity. We found that the T407A and S411A substitutions in NS3 reduce viral replication and increase the helicase-unwinding turnover rates by 1.7- and 3.5-fold, respectively, suggesting that flaviviruses may use suboptimal NS3 helicase activity for optimal genome replication. Additionally, we used simulations of each mutant to probe structural changes within NS3 caused by each mutation. These simulations indicate that Motif V controls communication between the ATP-binding pocket and the helical gate. These results help define the linkage between ATP hydrolysis and helicase activities within NS3 and provide insight into the biophysical mechanisms for ATPase-driven NS3 helicase function.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.