ArticleNature structural & molecular biology2019
Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule.
Article in Nature structural & molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 84 citations in OpenAlex.
- Halting translation by the letter with sequence-selective small molecules.Nature chemical biology · 2026Review
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- Approaches for Studying Context Specificity of Translation Inhibitor Action.International journal of molecular sciences · 2026Review
- Evolution of a core ribosomal innovation in octopus.bioRxiv : the preprint server for biology · 2026Article
- Context-dependent translation inhibition as a cancer therapeutic modality.Nature communications · 2026Article
- Sensitivity to an inhibitor of translation elongation in solid and hematologic cancers.Scientific reports · 2025Article
- Dysregulated ribosome quality control in human diseases.The FEBS journal · 2025Review
- RNA elements required for the high efficiency of West Nile virus-induced ribosomal frameshifting.Nucleic acids research · 2025Article
- Girolline is a sequence context-selective modulator of eIF5A activity.Nature communications · 2025Article
- SVC112: From Hummingbirds to Head and Neck Cancer.Advances in experimental medicine and biology · 2025Article
- Structural basis for translational control by the human 48S initiation complex.Nature structural & molecular biology · 2025Article
- Activity-Based DNA-Encoded Library Screening for Selective Inhibitors of Eukaryotic Translation.ACS central science · 2024Article
- Article
- The eRF1 degrader SRI-41315 acts as a molecular glue at the ribosomal decoding center.Nature chemical biology · 2024Article
- Puromycin reveals a distinct conformation of neuronal ribosomes.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- A highly efficient human cell-free translation system.RNA (New York, N.Y.) · 2023Article
- Clinical, genetic and structural delineation of RPL13-related spondyloepimetaphyseal dysplasia suggest extra-ribosomal functions of eL13.NPJ genomic medicine · 2023Article
- Cryo-electron microscopy structure and translocation mechanism of the crenarchaeal ribosome.Nucleic acids research · 2023Article
- Signal peptide mimicry primes Sec61 for client-selective inhibition.Nature chemical biology · 2023Article
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest.
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