ArticleeLife2022
Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes.
Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 27 citations in OpenAlex.
- Observing intersubunit dynamics in single yeast ribosomes.Nucleic acids research · 2026Article
- Review
- Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.Nature communications · 2025Article
- Oxidative stress sensing by the translation elongation machinery promotes production of detoxifying selenoproteins.bioRxiv : the preprint server for biology · 2025Article
- Structural mechanism of mRNA decoding by mammalian GTPase GTPBP1.bioRxiv : the preprint server for biology · 2025Article
- Targeting Eukaryotic Elongation Factor 1A: How Small-Molecule Inhibitors Suppress Tumor Growth via Diverse Pathways.International journal of molecular sciences · 2025Review
- Identification and Ranking of Binding Sites from Structural Ensembles: Application to SARS-CoV-2.Viruses · 2024Article
- The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center.Nature chemical biology · 2024Article
- Genome-wide analysis of the soybeanFrontiers in plant science · 2024Article
- How degrading! Trapped translation factors get trashed.Cell reports · 2023Article
- An automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics.Nature communications · 2023Article
- Sordarin bound eEF2 unlocks spontaneous forward and reverse translocation on CrPV IRES.Nucleic acids research · 2023Article
- Article
- Anticancer Small-Molecule Agents Targeting Eukaryotic Elongation Factor 1A: State of the Art.International journal of molecular sciences · 2023Review
- Article
- Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Rapid and accurate mRNA translation requires efficient codon-dependent delivery of the correct aminoacyl-tRNA (aa-tRNA) to the ribosomal A site. In mammals, this fidelity-determining reaction is facilitated by the GTPase elongation factor-1 alpha (eEF1A), which escorts aa-tRNA as an eEF1A(GTP)-aa-tRNA ternary complex into the ribosome. The structurally unrelated cyclic peptides didemnin B and ternatin-4 bind to the eEF1A(GTP)-aa-tRNA ternary complex and inhibit translation but have different effects on protein synthesis in vitro and in vivo. Here, we employ single-molecule fluorescence imaging and cryogenic electron microscopy to determine how these natural products inhibit translational elongation on mammalian ribosomes. By binding to a common site on eEF1A, didemnin B and ternatin-4 trap eEF1A in an intermediate state of aa-tRNA selection, preventing eEF1A release and aa-tRNA accommodation on the ribosome. We also show that didemnin B and ternatin-4 exhibit distinct effects on the dynamics of aa-tRNA selection that inform on observed disparities in their inhibition efficacies and physiological impacts. These integrated findings underscore the value of dynamics measurements in assessing the mechanism of small-molecule inhibition and highlight potential of single-molecule methods to reveal how distinct natural products differentially impact the human translation mechanism.
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