+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26035 | |||||||||||||||
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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 |
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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 / mammalian oogenesis stage / retinal ganglion cell axon guidance / 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 / mammalian oogenesis stage / retinal ganglion cell axon guidance / G1 to G0 transition / activation-induced cell death of T cells / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / phagocytic cup / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / TOR signaling / T cell proliferation involved in immune response / ribosomal small subunit export from nucleus / erythrocyte development / translation regulator activity / cellular response to actinomycin D / cytosolic ribosome / rough endoplasmic reticulum / 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) / gastrulation / MDM2/MDM4 family protein binding / DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest / negative regulation of ubiquitin-dependent protein catabolic process / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / rescue of stalled ribosome / 90S preribosome / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / maturation of SSU-rRNA / positive regulation of translation / small-subunit processome / positive regulation of apoptotic signaling pathway / protein kinase C binding / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / modification-dependent protein catabolic process / cytoplasmic ribonucleoprotein granule / spindle / G1/S transition of mitotic cell cycle / rRNA processing / protein tag activity / rhythmic process / positive regulation of canonical Wnt signaling pathway / ribosome binding / glucose homeostasis / retina development in camera-type eye / 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 / perikaryon / cytosolic small ribosomal subunit / cytosolic large ribosomal subunit / mitochondrial inner membrane / tRNA binding / cytoplasmic translation / postsynaptic density / cell differentiation / protein stabilization / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / ribonucleoprotein complex / cell cycle / translation / positive regulation of protein phosphorylation / positive regulation of apoptotic process / cell division / DNA repair / mRNA binding / apoptotic process / ubiquitin protein ligase binding / synapse / dendrite / positive regulation of cell population proliferation / positive regulation of gene expression / nucleolus / negative regulation of apoptotic process / protein kinase binding / perinuclear region of cytoplasm / Golgi apparatus / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum / DNA binding 類似検索 - 分子機能 | |||||||||||||||
生物種 | Oryctolagus cuniculus (ウサギ) / Saccharomyces cerevisiae (パン酵母) / Escherichia coli K-12 (大腸菌) / Homo sapiens (ヒト) | |||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.1 Å | |||||||||||||||
データ登録者 | Loveland AB / Svidritskiy E / Susorov D / Lee S / Park A / Zvornicanin S / Demo G / Gao FB / Korostelev AA | |||||||||||||||
資金援助 | 米国, 4件
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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. | |||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_26035.map.gz | 794.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26035-v30.xml emd-26035.xml | 99.5 KB 99.5 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_26035_fsc.xml | 20.7 KB | 表示 | FSCデータファイル |
画像 | emd_26035.png | 136.3 KB | ||
Filedesc metadata | emd-26035.cif.gz | 18.6 KB | ||
その他 | emd_26035_half_map_1.map.gz emd_26035_half_map_2.map.gz | 144.7 MB 144.7 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26035 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26035 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_26035_validation.pdf.gz | 929.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_26035_full_validation.pdf.gz | 929.2 KB | 表示 | |
XML形式データ | emd_26035_validation.xml.gz | 29.9 KB | 表示 | |
CIF形式データ | emd_26035_validation.cif.gz | 39.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26035 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-26035 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_26035.map.gz / 形式: CCP4 / 大きさ: 857.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | Rabbit 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein polyPR | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.87 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-ハーフマップ: Half map 2
ファイル | emd_26035_half_map_1.map | ||||||||||||
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注釈 | Half map 2 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half map 1
ファイル | emd_26035_half_map_2.map | ||||||||||||
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注釈 | Half map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
+全体 : Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide...
+超分子 #1: Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide...
+分子 #1: 18S rRNA
+分子 #2: 28S rRNA
+分子 #3: 5.8S rRNA
+分子 #4: 5S rRNA
+分子 #82: RNA (5'-R(*CP*AP*CP*AP*UP*GP*UP*UP*CP*C)-3')
+分子 #84: tRNAfMet
+分子 #5: uL2
+分子 #6: 60S ribosomal protein L3
+分子 #7: 60S ribosomal protein L4
+分子 #8: 60S ribosomal protein L5
+分子 #9: 60S ribosomal protein L6
+分子 #10: uL30
+分子 #11: eL8
+分子 #12: 60S ribosomal protein L9
+分子 #13: Ribosomal protein L10
+分子 #14: 60S ribosomal protein L11
+分子 #15: 60S ribosomal protein L12
+分子 #16: eL13
+分子 #17: 60S ribosomal protein L14
+分子 #18: 60S ribosomal protein L15
+分子 #19: uL13
+分子 #20: 60S ribosomal protein L17
+分子 #21: eL18
+分子 #22: 60S ribosomal protein L19
+分子 #23: eL20
+分子 #24: 60S ribosomal protein L21
+分子 #25: eL22
+分子 #26: 60S ribosomal protein L23
+分子 #27: Ribosomal protein L24
+分子 #28: uL23
+分子 #29: 60S ribosomal protein L26
+分子 #30: 60S ribosomal protein L27
+分子 #31: 60S ribosomal protein L27a
+分子 #32: eL29
+分子 #33: eL30
+分子 #34: 60S ribosomal protein L31
+分子 #35: 60S ribosomal protein L32
+分子 #36: 60S ribosomal protein L35a
+分子 #37: 60S ribosomal protein L34
+分子 #38: 60S ribosomal protein L35
+分子 #39: 60S ribosomal protein L36
+分子 #40: 60S ribosomal protein L37
+分子 #41: eL38
+分子 #42: eL39
+分子 #43: eL40
+分子 #44: eL41
+分子 #45: eL42
+分子 #46: 60S ribosomal protein L37a
+分子 #47: 60S acidic ribosomal protein P0
+分子 #48: Receptor of activated protein C kinase 1
+分子 #49: 40S_SA_C domain-containing protein
+分子 #50: 40S ribosomal protein S3a
+分子 #51: 40S ribosomal protein S2
+分子 #52: 40S ribosomal protein S3
+分子 #53: 40S ribosomal protein S4
+分子 #54: Ribosomal protein S5
+分子 #55: 40S ribosomal protein S6
+分子 #56: eS7
+分子 #57: 40S ribosomal protein S8
+分子 #58: 40S ribosomal protein S9
+分子 #59: 40S ribosomal protein S10
+分子 #60: 40S ribosomal protein S11
+分子 #61: 40S ribosomal protein S12
+分子 #62: 40S ribosomal protein S13
+分子 #63: 40S ribosomal protein S14
+分子 #64: 40S ribosomal protein S15
+分子 #65: uS9
+分子 #66: 40S ribosomal protein S17
+分子 #67: 40S ribosomal protein S18
+分子 #68: eS19
+分子 #69: 40S ribosomal protein S20
+分子 #70: eS21
+分子 #71: 40S ribosomal protein S15a
+分子 #72: 40S ribosomal protein S23
+分子 #73: 40S ribosomal protein S24
+分子 #74: 40S ribosomal protein S25
+分子 #75: eS26
+分子 #76: 40S ribosomal protein S27
+分子 #77: 40S ribosomal protein S28
+分子 #78: 40S ribosomal protein S29
+分子 #79: 40S ribosomal protein S30
+分子 #80: 40S ribosomal protein S27a
+分子 #81: 60S ribosomal protein L28
+分子 #83: PR20, ALS/FTD dipeptide repeat protein
+分子 #85: ZINC ION
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7 |
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凍結 | 凍結剤: ETHANE / チャンバー内湿度: 95 % |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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撮影 | フィルム・検出器のモデル: GATAN K3 (6k x 4k) / 平均電子線量: 30.0 e/Å2 |
電子線 | 加速電圧: 200 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1.8 µm / 最小 デフォーカス(公称値): 0.5 µm |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |