- EMDB-26033: Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide re... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-26033
タイトル
Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein GR20
マップデータ
Yeast 80S ribosome with heterogeneous 40S and GR bound to the peptide tunnel
試料
複合体: Yeast 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein GR20
RNA: x 4種
タンパク質・ペプチド: x 44種
リガンド: x 1種
機能・相同性
機能・相同性情報
hexon binding / pre-mRNA 5'-splice site binding / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / 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 / negative regulation of mRNA splicing, via spliceosome ...hexon binding / pre-mRNA 5'-splice site binding / cleavage in ITS2 between 5.8S rRNA and LSU-rRNA of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / response to cycloheximide / 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 / negative regulation of mRNA splicing, via spliceosome / preribosome, large subunit precursor / L13a-mediated translational silencing of Ceruloplasmin expression / ribosomal large subunit export from nucleus / 90S preribosome / regulation of translational fidelity / protein-RNA complex assembly / maturation of LSU-rRNA / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / macroautophagy / maintenance of translational fidelity / modification-dependent protein catabolic process / protein tag activity / rRNA processing / ribosome biogenesis / viral capsid / 5S rRNA binding / large ribosomal subunit rRNA binding / ribosomal large subunit assembly / cytoplasmic translation / cytosolic large ribosomal subunit / negative regulation of translation / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / translation / response to antibiotic / mRNA binding / ubiquitin protein ligase binding / host cell nucleus / nucleolus / RNA binding / nucleus / metal ion binding / cytosol / cytoplasm 類似検索 - 分子機能
60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / : / Pre-hexon-linking protein VIII / Adenovirus hexon associated protein, protein VIII / 50S ribosomal protein L10, insertion domain superfamily / : / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal protein L41 ...60s Acidic ribosomal protein / 60S acidic ribosomal protein P0 / : / Pre-hexon-linking protein VIII / Adenovirus hexon associated protein, protein VIII / 50S ribosomal protein L10, insertion domain superfamily / : / 60S ribosomal protein L10P, insertion domain / Insertion domain in 60S ribosomal protein L10P / Ribosomal protein L41 / Ribosomal protein L41 / Ribosomal protein L29e / Ribosomal L29e protein family / Ribosomal protein L13e, conserved site / Ribosomal protein L13e signature. / Ribosomal protein L22e / Ribosomal protein L22e superfamily / Ribosomal L22e protein family / Ribosomal protein L38e / Ribosomal protein L38e superfamily / Ribosomal L38e protein family / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein L44e signature. / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein L10e / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19, eukaryotic / 60S ribosomal protein L18a/ L20, eukaryotes / : / Ribosomal protein L24e, conserved site / Ribosomal protein L19/L19e conserved site / Ribosomal protein L19e signature. / Ribosomal protein L24e signature. / Ribosomal protein L44e / Ribosomal protein L44 / Ribosomal protein L34e, conserved site / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / : / Ribosomal protein L30e signature 1. / Ribosomal protein L6e signature. / 50S ribosomal protein L18Ae/60S ribosomal protein L20 and L18a / Ribosomal protein 50S-L18Ae/60S-L20/60S-L18A / Ribosomal L40e family / Ribosomal proteins 50S-L18Ae/60S-L20/60S-L18A / Ribosomal_L40e / Ribosomal protein L40e / Ribosomal protein L40e superfamily / Ribosomal protein L23/L25, N-terminal / Ribosomal protein L23, N-terminal domain / Ribosomal protein L30e signature 2. / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal protein L30e, conserved site / Ribosomal protein L27e / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal protein L36e signature. / Ribosomal protein L39e, conserved site / Ribosomal protein L39e signature. / Ribosomal protein L34Ae / Ribosomal protein L34e / Ribosomal protein L14e domain / Ribosomal protein L35Ae, conserved site / 60S ribosomal protein L19 / Ribosomal protein L14 / Ribosomal protein L35Ae signature. / Ribosomal protein L30/YlxQ / Ribosomal Protein L6, KOW domain / Ribosomal protein L7A/L8 / Ribosomal protein L13, eukaryotic/archaeal / 60S ribosomal protein L35 / Ribosomal protein L6e / 60S ribosomal protein L6E / Ribosomal protein L14 / Ribosomal protein L14, KOW motif / Ribosomal protein L37ae / Ribosomal L37ae protein family / 60S ribosomal protein L4, C-terminal domain / 60S ribosomal protein L4 C-terminal domain / Ribosomal protein L7, eukaryotic / Ribosomal protein L31e, conserved site / Ribosomal protein L31e signature. / Ribosomal_L19e / Ribosomal protein L30, N-terminal / Ribosomal L30 N-terminal domain / Ribosomal protein L19/L19e / Ribosomal protein L19/L19e, domain 1 / Ribosomal protein L19/L19e superfamily / Ribosomal protein L19e / Ribosomal protein L36e / Ribosomal protein L36e domain superfamily / Ribosomal protein L36e / Ribosomal protein L39e / Ribosomal protein L39e domain superfamily / Ribosomal L39 protein / Ribosomal protein L35A 類似検索 - ドメイン・相同性
RPL38 isoform 1 / RPL10 isoform 1 / 60S ribosomal protein L29 / RPL24A isoform 1 / RPL5 isoform 1 / RPL32 isoform 1 / RPL4A isoform 1 / Large ribosomal subunit protein uL3 / RPL11A isoform 1 / Large ribosomal subunit protein uL15 ...RPL38 isoform 1 / RPL10 isoform 1 / 60S ribosomal protein L29 / RPL24A isoform 1 / RPL5 isoform 1 / RPL32 isoform 1 / RPL4A isoform 1 / Large ribosomal subunit protein uL3 / RPL11A isoform 1 / Large ribosomal subunit protein uL15 / Large ribosomal subunit protein uL23 / Large ribosomal subunit protein eL39 / Large ribosomal subunit protein uL10 / 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 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 / Pre-hexon-linking protein VIII / Large ribosomal subunit protein eL19A / Large ribosomal subunit protein uL29A / Small ribosomal subunit protein eS32A / Large ribosomal subunit protein eL30 / Large ribosomal subunit protein eL8A / Large ribosomal subunit protein uL13A / Large ribosomal subunit protein eL14A / Large ribosomal subunit protein eL37A / Large ribosomal subunit protein eL34A / Large ribosomal subunit protein eL6A / Large ribosomal subunit protein eL21A / Large ribosomal subunit protein eL13A 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM107465
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
GM127094
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
NS101986
米国
引用
ジャーナル: Nat Commun / 年: 2022 タイトル: Ribosome inhibition by C9ORF72-ALS/FTD-associated poly-PR and poly-GR proteins revealed by cryo-EM. 著者: Anna B Loveland / Egor Svidritskiy / Denis Susorov / Soojin Lee / Alexander Park / Sarah Zvornicanin / Gabriel Demo / Fen-Biao Gao / Andrei A Korostelev / 要旨: Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). ...Toxic dipeptide-repeat (DPR) proteins are produced from expanded GC repeats in the C9ORF72 gene, the most common genetic cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Two DPR proteins, poly-PR and poly-GR, repress cellular translation but the molecular mechanism remains unknown. Here we show that poly-PR and poly-GR of ≥20 repeats inhibit the ribosome's peptidyl-transferase activity at nanomolar concentrations, comparable to specific translation inhibitors. High-resolution cryogenic electron microscopy (cryo-EM) reveals that poly-PR and poly-GR block the polypeptide tunnel of the ribosome, extending into the peptidyl-transferase center (PTC). Consistent with these findings, the macrolide erythromycin, which binds in the tunnel, competes with poly-PR and restores peptidyl-transferase activity. Our results demonstrate that strong and specific binding of poly-PR and poly-GR in the ribosomal tunnel blocks translation, revealing the structural basis of their toxicity in C9ORF72-ALS/FTD.