+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 7toq | |||||||||||||||
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タイトル | Mammalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein poly-PR | |||||||||||||||
要素 |
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キーワード | RIBOSOME / ribosomal binding peptide / ALS/FTD-associated dipeptide repeat protein | |||||||||||||||
機能・相同性 | 機能・相同性情報 ribosomal subunit / 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 ...ribosomal subunit / 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 / ubiquitin ligase inhibitor activity / phagocytic cup / 90S preribosome / TOR signaling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / T cell proliferation involved in immune response / erythrocyte development / cellular response to actinomycin D / negative regulation of ubiquitin-dependent protein catabolic process / ribosomal small subunit export from nucleus / translation regulator activity / 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 / cytosolic ribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / class I DNA-(apurinic or apyrimidinic site) endonuclease activity / DNA-(apurinic or apyrimidinic site) lyase / rescue of stalled ribosome / ribosomal large subunit biogenesis / maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / maturation of SSU-rRNA / positive regulation of translation / small-subunit processome / protein kinase C binding / positive regulation of apoptotic signaling pathway / positive regulation of protein-containing complex assembly / placenta development / cellular response to gamma radiation / mRNA 5'-UTR binding / transcription coactivator binding / spindle / cytoplasmic ribonucleoprotein granule / modification-dependent protein catabolic process / G1/S transition of mitotic cell cycle / protein tag activity / rRNA processing / ribosomal small subunit biogenesis / rhythmic process / positive regulation of canonical Wnt signaling pathway / small ribosomal subunit rRNA binding / ribosome binding / glucose homeostasis / regulation of translation / ribosomal small subunit assembly / retina development in camera-type eye / small ribosomal subunit / 5S rRNA binding / large ribosomal subunit rRNA binding / T cell differentiation in thymus / cytosolic small ribosomal subunit / ribosomal large subunit assembly / cell body / cytoplasmic translation / perikaryon / cytosolic large ribosomal subunit / tRNA binding / mitochondrial inner membrane / postsynaptic density / cell differentiation / protein stabilization / rRNA binding / ribosome / protein ubiquitination / structural constituent of ribosome / positive regulation of apoptotic process / positive regulation of protein phosphorylation / ribonucleoprotein complex / translation / cell division / DNA repair / mRNA binding / dendrite / ubiquitin protein ligase binding / positive regulation of cell population proliferation / synapse / positive regulation of gene expression / negative regulation of apoptotic process / nucleolus / apoptotic process / protein kinase binding / perinuclear region of cytoplasm / Golgi apparatus / negative regulation of transcription by RNA polymerase II / endoplasmic reticulum 類似検索 - 分子機能 | |||||||||||||||
生物種 | Oryctolagus cuniculus (ウサギ) Escherichia coli K-12 (大腸菌) Saccharomyces cerevisiae (パン酵母) Homo sapiens (ヒト) | |||||||||||||||
手法 | 電子顕微鏡法 / 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, A.B. / Svidritskiy, E. / Susorov, D. / Lee, S. / Park, A. / Zvornicanin, S. / Demo, G. / Gao, F.B. / Korostelev, A.A. | |||||||||||||||
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
構造ビューア | 分子: MolmilJmol/JSmol |
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-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 7toq.cif.gz | 4.7 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb7toq.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 7toq.json.gz | ツリー表示 | PDBx/mmJSON形式 | |
その他 | その他のダウンロード |
-検証レポート
文書・要旨 | 7toq_validation.pdf.gz | 1.9 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 7toq_full_validation.pdf.gz | 1.9 MB | 表示 | |
XML形式データ | 7toq_validation.xml.gz | 332.9 KB | 表示 | |
CIF形式データ | 7toq_validation.cif.gz | 585.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/to/7toq ftp://data.pdbj.org/pub/pdb/validation_reports/to/7toq | HTTPS FTP |
-関連構造データ
関連構造データ | 26035MC 7tooC 7topC 7torC 7tosC M: このデータのモデリングに利用したマップデータ C: 同じ文献を引用 (文献) |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
-RNA鎖 , 6種, 6分子 A18SA25SA58SA5SMRNAPTRN
#1: RNA鎖 | 分子量: 548024.188 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: GenBank: 6R6P_K |
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#2: RNA鎖 | 分子量: 1182428.000 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#3: RNA鎖 | 分子量: 50143.648 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#4: RNA鎖 | 分子量: 38691.914 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: GenBank: X06789.1 |
#82: RNA鎖 | 分子量: 3097.885 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Saccharomyces cerevisiae (パン酵母) |
#84: RNA鎖 | 分子量: 24802.785 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Escherichia coli K-12 (大腸菌) / 参照: GenBank: 1275521620 |
+タンパク質 , 21種, 21分子 AL02AL07AL08AL13AL16AL18AL20AL22AL25AL29AL30AL38AL40AL42ARACAS00AS07AS16AS19AS21AS26
+60S ribosomal protein ... , 25種, 25分子 AL03AL04AL05AL06AL09AL11AL12AL14AL15AL17AL19AL21AL23AL26AL27AL28AL31AL32AL33AL34AL35AL36AL37AL43EL28
-Ribosomal protein ... , 3種, 3分子 AL10AL24AS05
#13: タンパク質 | 分子量: 24511.861 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: B7NZQ2 |
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#27: タンパク質 | 分子量: 7512.774 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1SE28 |
#54: タンパク質 | 分子量: 21525.941 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) / 参照: UniProt: G1TFM5 |
-タンパク質・ペプチド , 4種, 4分子 AL39AL41ALP0PR
#42: タンパク質・ペプチド | 分子量: 6295.562 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
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#44: タンパク質・ペプチド | 分子量: 3213.075 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#47: タンパク質・ペプチド | 分子量: 3298.991 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Oryctolagus cuniculus (ウサギ) |
#83: タンパク質・ペプチド | 分子量: 5104.186 Da / 分子数: 1 / 由来タイプ: 合成 / 由来: (合成) Homo sapiens (ヒト) |
+40S ribosomal protein ... , 25種, 25分子 AS01AS02AS03AS04AS06AS08AS09AS10AS11AS12AS13AS14AS15AS17AS18AS20AS22AS23AS24AS25AS27AS28AS29AS30AS31
-非ポリマー , 1種, 4分子
#85: 化合物 | ChemComp-ZN / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
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EM実験 | 試料の集合状態: PARTICLE / 3次元再構成法: 単粒子再構成法 |
-試料調製
構成要素 | 名称: Mamalian 80S ribosome bound with the ALS/FTD-associated dipeptide repeat protein PR20 タイプ: RIBOSOME / Entity ID: #1-#84 / 由来: MULTIPLE SOURCES | ||||||||||||||||||||
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分子量 | 値: 4 MDa / 実験値: NO | ||||||||||||||||||||
由来(天然) |
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緩衝液 | pH: 7 | ||||||||||||||||||||
試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES | ||||||||||||||||||||
急速凍結 | 凍結剤: ETHANE / 湿度: 95 % |
-電子顕微鏡撮影
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TALOS ARCTICA |
電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 200 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 500 nm |
撮影 | 電子線照射量: 30 e/Å2 / フィルム・検出器のモデル: GATAN K3 (6k x 4k) |
-解析
EMソフトウェア | 名称: FREALIGN / バージョン: 9.11 / カテゴリ: 3次元再構成 |
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CTF補正 | タイプ: PHASE FLIPPING ONLY |
3次元再構成 | 解像度: 3.1 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 63475 / 対称性のタイプ: POINT |