regulation of polysaccharide biosynthetic process / transporter complex / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / lipopolysaccharide transport / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Formation of a pool of free 40S subunits ...regulation of polysaccharide biosynthetic process / transporter complex / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / lipopolysaccharide transport / SRP-dependent cotranslational protein targeting to membrane / GTP hydrolysis and joining of the 60S ribosomal subunit / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / Formation of a pool of free 40S subunits / preribosome, large subunit precursor / L13a-mediated translational silencing of Ceruloplasmin expression / Gram-negative-bacterium-type cell outer membrane assembly / translational elongation / ribosomal large subunit export from nucleus / regulation of translational fidelity / protein-RNA complex assembly / translational termination / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / macroautophagy / translational initiation / modification-dependent protein catabolic process / protein tag activity / maintenance of translational fidelity / cell outer membrane / rRNA processing / ribosome biogenesis / 5S rRNA binding / ribosomal large subunit assembly / large ribosomal subunit rRNA binding / cytosolic large ribosomal subunit / cytoplasmic translation / protein ubiquitination / negative regulation of translation / rRNA binding / structural constituent of ribosome / ribosome / translation / response to antibiotic / mRNA binding / ubiquitin protein ligase binding / nucleolus / RNA binding / zinc ion binding / nucleus / cytosol / cytoplasm 類似検索 - 分子機能
LptD, C-terminal / LPS-assembly protein LptD / : / LPS transport system D / Organic solvent tolerance-like, N-terminal / LptA/(LptD N-terminal domain) LPS transport protein / : / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L22e ...LptD, C-terminal / LPS-assembly protein LptD / : / LPS transport system D / Organic solvent tolerance-like, N-terminal / LptA/(LptD N-terminal domain) LPS transport protein / : / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L27e, conserved site / 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 / Ribosomal protein L44e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19, eukaryotic / Ribosomal protein L19e signature. / : / 60S ribosomal protein L18a/ L20, eukaryotes / Ribosomal protein L6e signature. / : / Ribosomal protein L44e / Ribosomal protein L44 / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal L18 C-terminal region / Ribosomal L40e family / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal protein 60S L18 and 50S L18e / 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 / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal Protein L6, KOW domain / Ribosomal protein L36e signature. / Ribosomal protein L35Ae, conserved site / Ribosomal protein L35Ae signature. / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / 60S ribosomal protein L19 / : / Ribosomal protein L13, eukaryotic/archaeal / Ribosomal protein L6e / Ribosomal protein L34Ae / Ribosomal protein L34e / Ribosomal protein L7A/L8 / 60S ribosomal protein L6E / 60S ribosomal protein L35 / Ribosomal protein L18e / Ribosomal protein L19e, C-terminal domain / Ribosomal_L19e / 60S ribosomal protein L4, C-terminal domain / 60S ribosomal protein L4 C-terminal domain / Ribosomal protein L19/L19e / Ribosomal protein L7, eukaryotic / Ribosomal protein L19/L19e, domain 1 / Ribosomal protein L31e, conserved site / Ribosomal protein L19/L19e superfamily / Ribosomal protein L19e, N-terminal domain / Ribosomal protein L31e signature. / Ribosomal protein L30, N-terminal / Ribosomal L30 N-terminal domain / Ribosomal protein L37ae / Ribosomal L37ae protein family / Ribosomal protein L36e / Ribosomal protein L36e domain superfamily / Ribosomal protein L36e / Ribosomal protein L14e domain / Ribosomal protein L14 / Ribosomal protein L35A / Ribosomal protein L35Ae / Ribosomal protein L39e / Ribosomal protein L39e domain superfamily / Ribosomal protein L35A superfamily / Ribosomal L39 protein / Ribosomal protein L32e, conserved site / Ribosomal protein L32e signature. / Ribosomal protein L5 eukaryotic/L18 archaeal / Ribosomal large subunit proteins 60S L5, and 50S L18 / Ribosomal protein L6, conserved site-2 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL15 / Large ribosomal subunit protein eL24A / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein uL30A / Large ribosomal subunit protein uL6A / Large ribosomal subunit protein uL22A / Large ribosomal subunit protein uL24A / Large ribosomal subunit protein eL33A / Large ribosomal subunit protein eL36A ...Large ribosomal subunit protein uL15 / Large ribosomal subunit protein eL24A / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein uL30A / Large ribosomal subunit protein uL6A / Large ribosomal subunit protein uL22A / Large ribosomal subunit protein uL24A / Large ribosomal subunit protein eL33A / Large ribosomal subunit protein eL36A / Large ribosomal subunit protein eL29 / Large ribosomal subunit protein eL15A / Large ribosomal subunit protein eL22A / Large ribosomal subunit protein eL27A / Large ribosomal subunit protein eL31A / Ubiquitin-ribosomal protein eL40A fusion protein / Large ribosomal subunit protein eL20A / Large ribosomal subunit protein eL43A / Large ribosomal subunit protein eL42A / Large ribosomal subunit protein uL14A / Large ribosomal subunit protein uL2A / Large ribosomal subunit protein eL18A / Large ribosomal subunit protein eL19A / Large ribosomal subunit protein uL29A / Large ribosomal subunit protein uL4A / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein eL8A / Large ribosomal subunit protein uL18 / Large ribosomal subunit protein uL13A / Large ribosomal subunit protein eL14A / Large ribosomal subunit protein eL32 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein eL37A / Large ribosomal subunit protein eL38 / Large ribosomal subunit protein eL34A / Large ribosomal subunit protein eL6A / Large ribosomal subunit protein eL21A / LPS-assembly protein LptD / Large ribosomal subunit protein uL5B 類似検索 - 構成要素
ジャーナル: Nat Commun / 年: 2021 タイトル: Context-specific action of macrolide antibiotics on the eukaryotic ribosome. 著者: Maxim S Svetlov / Timm O Koller / Sezen Meydan / Vaishnavi Shankar / Dorota Klepacki / Norbert Polacek / Nicholas R Guydosh / Nora Vázquez-Laslop / Daniel N Wilson / Alexander S Mankin / 要旨: Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of ...Macrolide antibiotics bind in the nascent peptide exit tunnel of the bacterial ribosome and prevent polymerization of specific amino acid sequences, selectively inhibiting translation of a subset of proteins. Because preventing translation of individual proteins could be beneficial for the treatment of human diseases, we asked whether macrolides, if bound to the eukaryotic ribosome, would retain their context- and protein-specific action. By introducing a single mutation in rRNA, we rendered yeast Saccharomyces cerevisiae cells sensitive to macrolides. Cryo-EM structural analysis showed that the macrolide telithromycin binds in the tunnel of the engineered eukaryotic ribosome. Genome-wide analysis of cellular translation and biochemical studies demonstrated that the drug inhibits eukaryotic translation by preferentially stalling ribosomes at distinct sequence motifs. Context-specific action markedly depends on the macrolide structure. Eliminating macrolide-arrest motifs from a protein renders its translation macrolide-tolerant. Our data illuminate the prospects of adapting macrolides for protein-selective translation inhibition in eukaryotic cells.