- EMDB-26037: E. coli 70S ribosomes bound with the ALS/FTD-associated dipeptide... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-26037
タイトル
E. coli 70S ribosomes bound with the ALS/FTD-associated dipeptide repeat protein PR20
マップデータ
E. coli 70S ribosome without tRNA and with peptidyl tunnel occupied by polyPR
試料
複合体: E. coli 70S ribosome bound with the ALS/FTD-associated dipeptide repeat protein PR20
タンパク質・ペプチド: x 53種
RNA: x 3種
キーワード
ribosomal binding peptide / ALS/FTD-associated dipeptide repeat protein / RIBOSOME
機能・相同性
機能・相同性情報
DnaA-L2 complex / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / mRNA 5'-UTR binding / small ribosomal subunit rRNA binding / large ribosomal subunit / regulation of translation / ribosomal small subunit assembly ...DnaA-L2 complex / negative regulation of DNA-templated DNA replication initiation / ribosome assembly / assembly of large subunit precursor of preribosome / cytosolic ribosome assembly / mRNA 5'-UTR binding / small ribosomal subunit rRNA binding / large ribosomal subunit / regulation of translation / ribosomal small subunit assembly / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / transferase activity / cytosolic small ribosomal subunit / ribosomal large subunit assembly / cytoplasmic translation / cytosolic large ribosomal subunit / tRNA binding / negative regulation of translation / rRNA binding / ribosome / structural constituent of ribosome / ribonucleoprotein complex / translation / response to antibiotic / mRNA binding / RNA binding / zinc ion binding / membrane / metal ion binding / cytosol / cytoplasm 類似検索 - 分子機能
Ribosomal protein L1, bacterial-type / Ribosomal protein L10, eubacterial, conserved site / Ribosomal protein L10 signature. / Ribosomal protein L10 / Ribosomal protein L1, conserved site / Ribosomal protein L1 signature. / Ribosomal protein L1 / Ribosomal protein L1, 3-layer alpha/beta-sandwich / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid ...Ribosomal protein L1, bacterial-type / Ribosomal protein L10, eubacterial, conserved site / Ribosomal protein L10 signature. / Ribosomal protein L10 / Ribosomal protein L1, conserved site / Ribosomal protein L1 signature. / Ribosomal protein L1 / Ribosomal protein L1, 3-layer alpha/beta-sandwich / Ribosomal protein L25, short-form / Ribosomal protein S14, bacterial/plastid / Ribosomal protein L1-like / Ribosomal protein L1/ribosomal biogenesis protein / Ribosomal protein L1p/L10e family / Ribosomal protein L11, bacterial-type / Ribosomal protein L31 type A / Ribosomal protein S16, conserved site / Ribosomal protein S16 signature. / Ribosomal protein L31 signature. / Ribosomal protein L31 / Ribosomal protein L31 superfamily / Ribosomal protein L31 / Ribosomal protein L21, conserved site / Ribosomal protein L21 signature. / Ribosomal protein L11, conserved site / Ribosomal protein L11 signature. / Ribosomal protein L10-like domain superfamily / Ribosomal protein L16 signature 1. / Ribosomal protein L10P / Ribosomal protein L10 / Ribosomal protein L6, conserved site / Ribosomal protein L6 signature 1. / Ribosomal protein L16, conserved site / Ribosomal protein L16 signature 2. / Ribosomal protein L9 signature. / Ribosomal protein L9, bacteria/chloroplast / Ribosomal protein L9, C-terminal / Ribosomal protein L9, C-terminal domain / Ribosomal protein L9, C-terminal domain superfamily / Ribosomal protein L17 signature. / Ribosomal L25p family / Ribosomal protein L25 / Ribosomal protein L11, N-terminal / Ribosomal protein L11, N-terminal domain / Ribosomal protein L11/L12 / Ribosomal protein L11, C-terminal / Ribosomal protein L11, C-terminal domain superfamily / Ribosomal protein L11/L12, N-terminal domain superfamily / Ribosomal protein L11, RNA binding domain / Ribosomal protein L11/L12 / Ribosomal protein L36 signature. / Ribosomal protein L28/L24 superfamily / Ribosomal protein L25/Gln-tRNA synthetase, N-terminal / Ribosomal protein L25/Gln-tRNA synthetase, anti-codon-binding domain superfamily / Ribosomal protein L32p, bacterial type / Ribosomal protein L9, N-terminal domain superfamily / Ribosomal protein L9 / Ribosomal protein L9, N-terminal / Ribosomal protein L9, N-terminal domain / Ribosomal protein L28 / Ribosomal protein L35, conserved site / Ribosomal protein L35 signature. / Ribosomal protein L33, conserved site / Ribosomal protein L33 signature. / Ribosomal protein L35, non-mitochondrial / Ribosomal protein L5, bacterial-type / Ribosomal protein L18, bacterial-type / Ribosomal protein L6, bacterial-type / Ribosomal protein L9/RNase H1, N-terminal / Ribosomal protein L19, conserved site / Ribosomal protein L19 signature. / Ribosomal protein S3, bacterial-type / Ribosomal protein S6, conserved site / Ribosomal protein S6 signature. / Ribosomal protein S19, bacterial-type / Ribosomal protein S13, bacterial-type / Ribosomal protein L36 / Ribosomal protein L36 superfamily / Ribosomal protein L36 / Ribosomal protein S7, bacterial/organellar-type / Ribosomal protein S11, bacterial-type / Ribosomal protein S20 / Ribosomal protein S20 superfamily / Ribosomal protein S20 / Ribosomal protein L20 signature. / Ribosomal protein S9, bacterial/plastid / Ribosomal protein L27, conserved site / Ribosomal protein L27 signature. / Ribosomal protein S4, bacterial-type / 30S ribosomal protein S17 / Ribosomal protein S5, bacterial-type / Ribosomal protein L14P, bacterial-type / Ribosomal protein S6, plastid/chloroplast / Ribosomal protein L22, bacterial/chloroplast-type / Ribosomal protein L2, bacterial/organellar-type / Ribosomal protein S2, bacteria/mitochondria/plastid / Ribosomal protein L35 / Ribosomal protein L35 superfamily / Ribosomal protein L35 / Ribosomal protein L34, conserved site / Ribosomal L28 family 類似検索 - ドメイン・相同性
Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS17 / 50S ribosomal protein L35 / Large ribosomal subunit protein bL36 / Large ribosomal subunit protein bL28 / Small ribosomal subunit protein uS13 / 30S ribosomal protein S9 / 50S ribosomal protein L11 / 30S ribosomal protein S3 / Large ribosomal subunit protein uL5 ...Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS17 / 50S ribosomal protein L35 / Large ribosomal subunit protein bL36 / Large ribosomal subunit protein bL28 / Small ribosomal subunit protein uS13 / 30S ribosomal protein S9 / 50S ribosomal protein L11 / 30S ribosomal protein S3 / Large ribosomal subunit protein uL5 / 50S ribosomal protein L1 / Small ribosomal subunit protein uS10 / 50S ribosomal protein L10 / 50S ribosomal protein L18 / 50S ribosomal protein L27 / 50S ribosomal protein L19 / Large ribosomal subunit protein bL17 / Large ribosomal subunit protein bL21 / 50S ribosomal protein L30 / 30S ribosomal protein S14 / 50S ribosomal protein L24 / Ribosomal protein S21 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein bL34 / Small ribosomal subunit protein bS16 / Small ribosomal subunit protein uS2 / Small ribosomal subunit protein bS20 / Large ribosomal subunit protein uL29 / Large ribosomal subunit protein bL25 / Small ribosomal subunit protein uS15 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein bS18 / Small ribosomal subunit protein uS5 / Small ribosomal subunit protein uS11 / Small ribosomal subunit protein uS12 / 50S ribosomal protein L33 / 50S ribosomal protein L4 / 50S ribosomal protein L20 / 30S ribosomal protein S4 / Small ribosomal subunit protein bS6 / Small ribosomal subunit protein uS7 / Large ribosomal subunit protein uL16 / Large ribosomal subunit protein uL2 / Large ribosomal subunit protein uL3 / Large ribosomal subunit protein uL22 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein uL13 / 50S ribosomal protein L32 / Large ribosomal subunit protein uL14 / 50S ribosomal protein L23 / Large ribosomal subunit protein bL31 / Large ribosomal subunit protein bL9 類似検索 - 構成要素
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R01GM107465
米国
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)
R35GM127094
米国
National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS)
R01NS101986
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.