- EMDB-26035: Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptid... -
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基本情報
登録情報
データベース: EMDB / ID: EMD-26035
タイトル
Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein poly-PR
マップデータ
Rabbit 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein polyPR
試料
複合体: Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein PR20
RNA: x 6種
タンパク質・ペプチド: x 78種
リガンド: x 1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
regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / retinal ganglion cell axon guidance / mammalian oogenesis stage / G1 to G0 transition ...regulation of G1 to G0 transition / exit from mitosis / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / retinal ganglion cell axon guidance / mammalian oogenesis stage / G1 to G0 transition / activation-induced cell death of T cells / positive regulation of signal transduction by p53 class mediator / phagocytic cup / ubiquitin ligase inhibitor activity / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / 90S preribosome / T cell proliferation involved in immune response / erythrocyte development / negative regulation of ubiquitin-dependent protein catabolic process / translation regulator activity / cellular response to actinomycin D / ribosomal small subunit export from nucleus / cytosolic ribosome / endonucleolytic cleavage in ITS1 to separate SSU-rRNA from 5.8S rRNA and LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / rough endoplasmic reticulum / gastrulation / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / rescue of stalled ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / positive regulation of apoptotic signaling pathway / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA / small-subunit processome / positive regulation of translation / protein kinase C binding / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / transcription coactivator binding / mRNA 5'-UTR binding / modification-dependent protein catabolic process / spindle / cytoplasmic ribonucleoprotein granule / rRNA processing / G1/S transition of mitotic cell cycle / protein tag activity / positive regulation of canonical Wnt signaling pathway / rhythmic process / ribosome binding / retina development in camera-type eye / glucose homeostasis / regulation of translation / ribosomal small subunit biogenesis / ribosomal small subunit assembly / small ribosomal subunit / small ribosomal subunit rRNA binding / cell body / T cell differentiation in thymus / 5S rRNA binding / large ribosomal subunit rRNA binding / cytosolic small ribosomal subunit / perikaryon / cytosolic large ribosomal subunit / cytoplasmic translation / mitochondrial inner membrane / tRNA binding / postsynaptic density / cell differentiation / protein stabilization / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / translation / positive regulation of protein phosphorylation / positive regulation of apoptotic process / cell division / DNA repair / mRNA binding / ubiquitin protein ligase binding / synapse / dendrite / positive regulation of cell population proliferation / positive regulation of gene expression / nucleolus / negative regulation of apoptotic process / apoptotic process / protein kinase binding / perinuclear region of cytoplasm / Golgi apparatus / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / DNA binding / RNA binding 類似検索 - 分子機能
40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / : ...40S ribosomal protein SA, C-terminal domain / 40S ribosomal protein SA C-terminus / Ribosomal protein L6, N-terminal / Ribosomal protein L6, N-terminal domain / Ubiquitin-like protein FUBI / Ribosomal protein L28e / Ribosomal L15/L27a, N-terminal / Ribosomal L28e/Mak16 / Ribosomal L28e protein family / : / Ribosomal protein S26e signature. / : / Ribosomal protein S26e / Ribosomal protein S26e superfamily / Ribosomal protein S26e / Ribosomal protein S21e, conserved site / Ribosomal protein S21e signature. / metallochaperone-like domain / Ribosomal protein S12e signature. / TRASH domain / Ribosomal protein S12e / Small (40S) ribosomal subunit Asc1/RACK1 / Ribosomal protein S21e / Ribosomal protein S2, eukaryotic / Ribosomal protein S21e superfamily / Ribosomal protein S21e / S27a-like superfamily / 40S Ribosomal protein S10 / Ribosomal protein S10, eukaryotic/archaeal / Plectin/S10, N-terminal / Plectin/S10 domain / Ribosomal protein S25 / S25 ribosomal protein / Ribosomal protein S27a / Ribosomal protein S2, eukaryotic/archaeal / : / Ribosomal protein S27a / Ribosomal protein S27a / Ribosomal protein L27e, conserved site / Ribosomal protein L27e signature. / Ribosomal protein S17e, conserved site / Ribosomal protein S17e signature. / Ribosomal protein L44e signature. / Ribosomal protein S8e subdomain, eukaryotes / Ribosomal protein L10e, conserved site / Ribosomal protein L10e signature. / Ribosomal protein S30 / Ribosomal protein S30 / Ribosomal protein L10e / 40S ribosomal protein S29/30S ribosomal protein S14 type Z / Ribosomal protein L13e / Ribosomal protein L13e / Ribosomal protein L19, eukaryotic / Ribosomal protein S3, eukaryotic/archaeal / : / : / Ribosomal protein S3Ae, conserved site / Ribosomal protein S3Ae signature. / Ribosomal protein S27e signature. / Ribosomal protein L24e, conserved site / Ribosomal protein L24e signature. / Ribosomal protein L44e / Ribosomal protein S4e, N-terminal, conserved site / Ribosomal protein L19/L19e conserved site / Ribosomal protein L44 / Ribosomal protein L19e signature. / Ribosomal protein S4e signature. / Ribosomal protein L34e, conserved site / 40S ribosomal protein S4, C-terminal domain / 40S ribosomal protein S4 C-terminus / Ribosomal protein L34e signature. / Ribosomal protein L5 eukaryotic, C-terminal / Ribosomal L18 C-terminal region / Ribosomal protein S19A/S15e / Ribosomal protein S8e, conserved site / Ribosomal protein S8e signature. / Ribosomal protein L6e signature. / Ribosomal protein S17e / Ribosomal protein S17e-like superfamily / Ribosomal S17 / Eukaryotic Ribosomal Protein L27, KOW domain / Ribosomal protein S6, eukaryotic / Ribosomal protein S4e, N-terminal / RS4NT (NUC023) domain / Ribosomal protein L27e / 40S ribosomal protein S1/3, eukaryotes / Ribosomal protein L27e superfamily / Ribosomal L27e protein family / Ribosomal S24e conserved site / Ribosomal protein S24e signature. / Ribosomal protein L36e signature. / 40S ribosomal protein S11, N-terminal / Ribosomal_S17 N-terminal / Ribosomal protein L34Ae / Ribosomal protein L34e / 60S ribosomal protein L19 / Ribosomal protein S4, KOW domain / Ribosomal protein L35Ae, conserved site / Ribosomal protein L35Ae signature. / Ribosomal protein S4e 類似検索 - ドメイン・相同性
Large ribosomal subunit protein eL42 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL21 ...Large ribosomal subunit protein eL42 / Large ribosomal subunit protein uL4 / Large ribosomal subunit protein uL16 / Small ribosomal subunit protein uS4 / Large ribosomal subunit protein uL22 / Large ribosomal subunit protein eL24 / Large ribosomal subunit protein eL33 / Small ribosomal subunit protein eS12 / Large ribosomal subunit protein eL31 / Large ribosomal subunit protein eL21 / Large ribosomal subunit protein uL29 / Small ribosomal subunit protein uS10 / Small ribosomal subunit protein RACK1 / Ubiquitin-ribosomal protein eS31 fusion protein / Large ribosomal subunit protein eL6 / Large ribosomal subunit protein uL11 / Large ribosomal subunit protein uL15 / Small ribosomal subunit protein uS15 / Large ribosomal subunit protein uL24 / Small ribosomal subunit protein eS1 / Large ribosomal subunit protein uL6 / Large ribosomal subunit protein eL43 / Large ribosomal subunit protein uL18 / Small ribosomal subunit protein uS12 / Large ribosomal subunit protein eL15 / 40S ribosomal protein S24 / Large ribosomal subunit protein uL14 / Ubiquitin-like FUBI-ribosomal protein eS30 fusion protein / 40S ribosomal protein S4 / Small ribosomal subunit protein eS25 / Small ribosomal subunit protein eS26 / Small ribosomal subunit protein uS7 / Small ribosomal subunit protein uS8 / Small ribosomal subunit protein eS28 / 40S ribosomal protein SA / Small ribosomal subunit protein eS8 / Large ribosomal subunit protein eL13 / Large ribosomal subunit protein uL3 / Small ribosomal subunit protein eS6 / Small ribosomal subunit protein eS21 / Small ribosomal subunit protein uS3 / Small ribosomal subunit protein uS13 / Small ribosomal subunit protein eS10 / Small ribosomal subunit protein uS17 / Large ribosomal subunit protein eL36 / Small ribosomal subunit protein eS17 / Large ribosomal subunit protein uL5 / Large ribosomal subunit protein uL30 / Large ribosomal subunit protein eL27 / Large ribosomal subunit protein eL34 / Large ribosomal subunit protein eL19 / Small ribosomal subunit protein eS27 / Small ribosomal subunit protein uS19 / Large ribosomal subunit protein eL32 / Small ribosomal subunit protein uS11 / Large ribosomal subunit protein eL28 / Small ribosomal subunit protein uS14 / Large ribosomal subunit protein eL14 / Large ribosomal subunit protein eL37 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.