ArticleProceedings of the National Academy of Sciences of the United States of America2017
Aminoglycoside interactions and impacts on the eukaryotic ribosome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers.
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Who cites it
126 citing papers in PubMed, 207 citations in OpenAlex.
- Efficacy and safety of ataluren in patients with nonsense-mutation cystic fibrosis not receiving chronic inhaled aminoglycosides: The international, randomized, double-blind, placebo-controlled Ataluren Confirmatory Trial in Cystic Fibrosis (ACT CF).Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2020Trial
- Programmed repair of disease-causing UGA premature termination codons in mammalian brain.Nucleic acids research · 2026Article
- RiboScreenBiomedicines · 2026Review
- Observing intersubunit dynamics in single yeast ribosomes.Nucleic acids research · 2026Article
- Natural Products Beyond Inhibition: A Mechanistic Framework Spanning Pockets, Interfaces, and Kinetic Barriers.Molecules (Basel, Switzerland) · 2026Review
- Structure of the hibernating Francisella tularensis ribosome and mechanistic insights into its inhibition by antibiotics.Nucleic acids research · 2026Article
- Comparative evaluation of TRIDs : a strategy to improve treatments.Journal of translational medicine · 2026Article
- Camel plasma as an innovative non-antibiotic therapy forVeterinary world · 2026Article
- Effects of prey quality through the life cycle of the social amoeba Dictyostelium discoideum.BMC molecular and cell biology · 2026Article
- Penicillin-Streptomycin Treatment Rewires Core Metabolic and Ribosomal Programs in HepG2 Cells.Journal of proteome research · 2026Article
- Recovery of α-L-fucosidase in fucosidosis nonsense variants by readthrough stimulation and release factor degradation.Disease models & mechanisms · 2026Article
- CFTR rescue in W1282X cystic fibrosis patient-derived intestinal organoids (PDIOs) mediated by translational readthrough-inducing drugs (TRIDs).Genetics in medicine open · 2026Article
- Evolution of ribosome X-ray crystallography: from first crystals to atomic resolution.Biophysical reviews · 2025Review
- PP6 phosphatase and Elongator contribute to kinesin 5-dependent spindle assembly by controlling microtubule regulators levels.PLoS genetics · 2025Article
- Optimization of selection agent concentrations and expanding G418 utility for gentamicin resistance in Marchantia polymorpha.Scientific reports · 2025Article
- High-fidelity and differential nonsense suppression in live cells and a frontotemporal dementia allele with human transfer RNAs.Nucleic acids research · 2025Article
- Selective [9-Chembiochem : a European journal of chemical biology · 2025Article
- The commonly used antibiotic streptomycin reduces protein synthesis and differentiation in cultured C2C12 myotubes.Physiological reports · 2025Article
- Ribosomal expansion segment contributes to translation fidelity via N-terminal processing of ribosomal proteins.Nucleic acids research · 2025Article
- Mechanism of read-through enhancement by aminoglycosides and mefloquine.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
66 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 7 institutions in 2 countries.
Funding
Abstract
Aminoglycosides are chemically diverse, broad-spectrum antibiotics that target functional centers within the bacterial ribosome to impact all four principle stages (initiation, elongation, termination, and recycling) of the translation mechanism. The propensity of aminoglycosides to induce miscoding errors that suppress the termination of protein synthesis supports their potential as therapeutic interventions in human diseases associated with premature termination codons (PTCs). However, the sites of interaction of aminoglycosides with the eukaryotic ribosome and their modes of action in eukaryotic translation remain largely unexplored. Here, we use the combination of X-ray crystallography and single-molecule FRET analysis to reveal the interactions of distinct classes of aminoglycosides with the 80S eukaryotic ribosome. Crystal structures of the 80S ribosome in complex with paromomycin, geneticin (G418), gentamicin, and TC007, solved at 3.3- to 3.7-Å resolution, reveal multiple aminoglycoside-binding sites within the large and small subunits, wherein the 6'-hydroxyl substituent in ring I serves as a key determinant of binding to the canonical eukaryotic ribosomal decoding center. Multivalent binding interactions with the human ribosome are also evidenced through their capacity to affect large-scale conformational dynamics within the pretranslocation complex that contribute to multiple aspects of the translation mechanism. The distinct impacts of the aminoglycosides examined suggest that their chemical composition and distinct modes of interaction with the ribosome influence PTC read-through efficiency. These findings provide structural and functional insights into aminoglycoside-induced impacts on the eukaryotic ribosome and implicate pleiotropic mechanisms of action beyond decoding.
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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.