filamentous growth of a population of unicellular organisms in response to neutral pH / cellular response to neutral pH / filamentous growth of a population of unicellular organisms in response to biotic stimulus / filamentous growth of a population of unicellular organisms in response to starvation / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / yeast-form cell wall / regulation of cytoplasmic translation / GCN2-mediated signaling / invasive growth in response to glucose limitation ...filamentous growth of a population of unicellular organisms in response to neutral pH / cellular response to neutral pH / filamentous growth of a population of unicellular organisms in response to biotic stimulus / filamentous growth of a population of unicellular organisms in response to starvation / negative regulation of cell integrity MAPK cascade / positive regulation of conjugation with cellular fusion / yeast-form cell wall / regulation of cytoplasmic translation / GCN2-mediated signaling / invasive growth in response to glucose limitation / hyphal cell wall / preribosome / ribosome hibernation / negative regulation of p38MAPK cascade / filamentous growth / regulation of amino acid metabolic process / negative regulation of glucose mediated signaling pathway / positive regulation of translational fidelity / ribosome-associated ubiquitin-dependent protein catabolic process / GDP-dissociation inhibitor activity / pre-mRNA 5'-splice site binding / preribosome, small subunit precursor / nonfunctional rRNA decay / mRNA destabilization / negative regulation of translational frameshifting / negative regulation of mRNA splicing, via spliceosome / signaling receptor activator activity / translational elongation / G-protein alpha-subunit binding / 90S preribosome / ribosomal subunit export from nucleus / protein-RNA complex assembly / ribosomal small subunit export from nucleus / translation regulator activity / protein-membrane adaptor activity / DNA-(apurinic or apyrimidinic site) endonuclease activity / positive regulation of autophagy / rescue of stalled ribosome / protein kinase C binding / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / cellular response to starvation / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / small-subunit processome / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / extracellular vesicle / ribosome biogenesis / large ribosomal subunit / ribosome binding / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / 5S rRNA binding / ribosomal large subunit assembly / cytosolic small ribosomal subunit / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / cell adhesion / negative regulation of translation / rRNA binding / protein ubiquitination / structural constituent of ribosome / ribosome / G protein-coupled receptor signaling pathway / translation / ribonucleoprotein complex / mRNA binding / ubiquitin protein ligase binding / nucleolus / cell surface / RNA binding / extracellular region / zinc ion binding / metal ion binding / nucleus / cytosol / cytoplasm 類似検索 - 分子機能
: / Ribosomal protein L19e, C-terminal domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily ...: / Ribosomal protein L19e, C-terminal domain / : / Ribosomal protein S26e signature. / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / : / Ribosomal protein S12e signature. / Ribosomal protein S12e / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein S5, eukaryotic/archaeal / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S21e / Ribosomal protein S21e superfamily / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / Ribosomal protein L27e, conserved site / S27a-like superfamily / Ribosomal protein L27e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L10e / 40S Ribosomal protein S10 / : / Ribosomal protein L44e signature. / Ribosomal protein S7e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19, eukaryotic / Ribosomal protein L19e signature. / Plectin/S10, N-terminal / Plectin/S10 domain / : / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein L6e signature. / Ribosomal protein S10, eukaryotic/archaeal / Ribosomal protein S8e subdomain, eukaryotes / : / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein L44e / Ribosomal protein S3Ae, conserved site / Ribosomal protein L44 / Ribosomal protein S3Ae signature. / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein S2, eukaryotic/archaeal / Ribosomal protein L5 eukaryotic, C-terminal / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal L40e family / Ribosomal L18 C-terminal region / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein 60S L18 and 50S L18e / Ribosomal protein L30e signature 1. / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily / Ribosomal protein L18/L18-A/B/e, conserved site / Ribosomal protein L18e signature. / Ribosomal protein L23/L25, N-terminal / : / Ribosomal protein L23, N-terminal domain / Ribosomal protein S27e signature. / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein S4e signature. / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein S3, eukaryotic/archaeal / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal Protein L6, KOW domain / Ribosomal protein L36e signature. / Ribosomal protein L35Ae, conserved site / Ribosomal protein L30e signature 2. / Ribosomal protein L35Ae signature. / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family 類似検索 - ドメイン・相同性
Small ribosomal subunit protein eS4 / Large ribosomal subunit protein eL37 / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL40 / Large ribosomal subunit protein eL30 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL43 / Small ribosomal subunit protein eS30 ...Small ribosomal subunit protein eS4 / Large ribosomal subunit protein eL37 / Large ribosomal subunit protein eL38 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein eL19 / Large ribosomal subunit protein eL40 / Large ribosomal subunit protein eL30 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL43 / Small ribosomal subunit protein eS30 / Small ribosomal subunit protein uS14 / 60S ribosomal protein L42-B / Ribosomal protein S7 / 40S ribosomal protein S17-B / 40S ribosomal protein S26 / Ribosomal protein L22 / 60S ribosomal protein L7-A / 60S ribosomal protein L28 / 60S ribosomal protein L33-A / 40S ribosomal protein S27 / 40S ribosomal protein S10-A / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein uS3 / 40S ribosomal protein S6 / Ribosomal protein L13 / Small ribosomal subunit protein uS5 / 60S ribosomal protein L20 / 40S ribosomal protein S28-B / 60S ribosomal protein L8 / Small ribosomal subunit protein eS1 / Small ribosomal subunit protein uS2 / 40S ribosomal protein S12 / 40S ribosomal protein S24 / 60S ribosomal protein L9-B / 60S ribosomal protein L23-A / 60S ribosomal protein L24-A / 60S ribosomal protein L18-A / 40S ribosomal protein S19-A / 40S ribosomal protein S7 / 40S ribosomal protein S25 / 60S ribosomal protein L29 / 40S ribosomal protein S22-A / 40S ribosomal protein S8 / Ribosomal protein S23 (S12) / Small ribosomal subunit protein uS11 / 60S ribosomal protein L34-B / 60S ribosomal protein L21-A / 60S ribosomal protein L31-B / 60S ribosomal protein L11-B / Ribosomal protein S4 / 60S ribosomal protein L2-B / 60S ribosomal protein L14-B / Ribosomal protein L24 / 40S ribosomal protein S18-B / 40S ribosomal protein S13 / 60S ribosomal protein L4-B / 60S ribosomal protein L13 / Large ribosomal subunit protein uL23 / Ribosomal protein L29 / Large ribosomal subunit protein eL32 / Small ribosomal subunit protein uS9 / Large ribosomal subunit protein eL36 / Small ribosomal subunit protein RACK1 / Small ribosomal subunit protein eS32 / Large ribosomal subunit protein uL3 / Ubiquitin-ribosomal protein eS31 fusion protein / Large ribosomal subunit protein eL15 / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein eL39 / 60S ribosomal protein L6 / Large ribosomal subunit protein eL27 / Small ribosomal subunit protein eS21 類似検索 - 構成要素
ジャーナル: Proc Natl Acad Sci U S A / 年: 2025 タイトル: Mechanism of read-through enhancement by aminoglycosides and mefloquine. 著者: Olga Kolosova / Yury Zgadzay / Artem Stetsenko / Anastasia P Sukhinina / Anastasia Atamas / Shamil Validov / Andrey Rogachev / Konstantin Usachev / Lasse Jenner / Sergey E Dmitriev / Gulnara ...著者: Olga Kolosova / Yury Zgadzay / Artem Stetsenko / Anastasia P Sukhinina / Anastasia Atamas / Shamil Validov / Andrey Rogachev / Konstantin Usachev / Lasse Jenner / Sergey E Dmitriev / Gulnara Yusupova / Albert Guskov / Marat Yusupov / 要旨: Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of ...Nonsense mutations are associated with numerous and diverse pathologies, yet effective treatment strategies remain elusive. A promising approach to combat these conditions involves the use of aminoglycosides, particularly in combination with stop-codon read-through enhancers, for developing drugs that can rescue the production of full-length proteins. Using X-ray crystallography and single-particle cryo-EM, we obtained structures of the eukaryotic ribosome in complexes with several aminoglycosides (geneticin G418, paromomycin, and hygromycin B) and the antimalarial drug mefloquine (MFQ), which has also been identified as a read-through enhancer. Our study reveals a binding site of MFQ, which holds significant promise for the development of therapies targeting premature termination codon-related genetic and oncological diseases. The results underscore the crucial role of the bridge B7b/c in mediating the effects of MFQ on subunit rotation dynamics. Through a comprehensive analysis of the interactions between the drugs and the eukaryotic ribosome, we propose a unifying hypothesis for read-through enhancement by small molecules, highlighting the role of decoding center rearrangements and intersubunit rotation dynamics.