+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0599 | |||||||||
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タイトル | Structure of a drug-like molecule stalled CDH1 ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA | |||||||||
マップデータ | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA;map is sharpened. | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response ...response to Gram-positive bacterium / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / pituitary gland development / gamma-catenin binding / cell-cell adhesion mediated by cadherin / negative regulation of axon extension / cellular response to indole-3-methanol / flotillin complex / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / eukaryotic 80S initiation complex / protein tyrosine kinase inhibitor activity / Formation of definitive endoderm / negative regulation of protein neddylation / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / translation at presynapse / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of respiratory burst involved in inflammatory response / positive regulation of gastrulation / axial mesoderm development / regulation of G1 to G0 transition / negative regulation of formation of translation preinitiation complex / IRE1-RACK1-PP2A complex / nucleolus organization / ribosomal protein import into nucleus / 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 / response to extracellular stimulus / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / exit from mitosis / protein-DNA complex disassembly / TNFR1-mediated ceramide production / 90S preribosome assembly / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / negative regulation of RNA splicing / negative regulation of DNA repair / laminin receptor activity / optic nerve development / Adherens junctions interactions / TORC2 complex binding / catenin complex / Apoptotic cleavage of cell adhesion proteins / oxidized purine DNA binding / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / supercoiled DNA binding / GAIT complex / G1 to G0 transition / neural crest cell differentiation / retinal ganglion cell axon guidance / rRNA modification in the nucleus and cytosol / negative regulation of phagocytosis / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / cell-cell junction assembly / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / GTPase activating protein binding / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / adherens junction organization / A band / positive regulation of signal transduction by p53 class mediator / ubiquitin ligase inhibitor activity / alpha-beta T cell differentiation / 顔料 / protein kinase A binding / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / apical junction complex / ankyrin binding / Translation initiation complex formation / phagocytic cup / positive regulation of mitochondrial depolarization / response to aldosterone / negative regulation of Wnt signaling pathway / homeostatic process / positive regulation of T cell receptor signaling pathway / lung morphogenesis / macrophage chemotaxis / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of cell-cell adhesion / regulation of cell division / cellular response to lithium ion / SARS-CoV-1 modulates host translation machinery / homophilic cell adhesion via plasma membrane adhesion molecules / ヒドロキシル化 / iron-sulfur cluster binding / MTOR / BH3 domain binding / mTORC1-mediated signalling / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) 類似検索 - 分子機能 | |||||||||
生物種 | 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: 3.9 Å | |||||||||
データ登録者 | Li W / Cate JHD | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Nat Struct Mol Biol / 年: 2019 タイトル: Structural basis for selective stalling of human ribosome nascent chain complexes by a drug-like molecule. 著者: Wenfei Li / Fred R Ward / Kim F McClure / Stacey Tsai-Lan Chang / Elizabeth Montabana / Spiros Liras / Robert G Dullea / Jamie H D Cate / 要旨: The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ...The drug-like molecule PF-06446846 (PF846) binds the human ribosome and selectively blocks the translation of a small number of proteins by an unknown mechanism. In structures of PF846-stalled human ribosome nascent chain complexes, PF846 binds in the ribosome exit tunnel in a eukaryotic-specific pocket formed by 28S ribosomal RNA, and alters the path of the nascent polypeptide chain. PF846 arrests the translating ribosome in the rotated state of translocation, in which the peptidyl-transfer RNA 3'-CCA end is improperly docked in the peptidyl transferase center. Selections of messenger RNAs from mRNA libraries using translation extracts reveal that PF846 can stall translation elongation, arrest termination or even enhance translation, depending on nascent chain sequence context. These results illuminate how a small molecule selectively targets translation by the human ribosome, and provides a foundation for developing small molecules that modulate the production of proteins of therapeutic interest. | |||||||||
履歴 |
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-構造の表示
ムービー |
ムービービューア |
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構造ビューア | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_0599.map.gz | 228.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0599-v30.xml emd-0599.xml | 16.6 KB 16.6 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_0599_fsc.xml | 14.1 KB | 表示 | FSCデータファイル |
画像 | emd_0599.png | 348.5 KB | ||
その他 | emd_0599_additional.map.gz emd_0599_half_map_1.map.gz emd_0599_half_map_2.map.gz | 193.8 MB 194.6 MB 194.6 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0599 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0599 | HTTPS FTP |
-関連構造データ
関連構造データ | 6olfMC 0526C 0596C 0597C 0598C 0600C 0601C 6oleC 6olgC 6oliC 6olzC 6om0C 6om7C C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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類似構造データ |
-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_0599.map.gz / 形式: CCP4 / 大きさ: 244.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA;map is sharpened. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.15 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: PF846 stalled human ribosome nascent chain complex (CDH1-RNC)...
ファイル | emd_0599_additional.map | ||||||||||||
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注釈 | PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA;map is not sharpened. | ||||||||||||
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 of PF846 stalled human ribosome nascent...
ファイル | emd_0599_half_map_1.map | ||||||||||||
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注釈 | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA. | ||||||||||||
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 of PF846 stalled human ribosome nascent...
ファイル | emd_0599_half_map_2.map | ||||||||||||
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注釈 | Half map of PF846 stalled human ribosome nascent chain complex (CDH1-RNC) in rotated state with AA tRNA and PE tRNA. | ||||||||||||
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 : human ribosome nascent chain complex (CDH1-RNC) stalled by a drug...
全体 | 名称: human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AA tRNA and PE tRNA |
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要素 |
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-超分子 #1: human ribosome nascent chain complex (CDH1-RNC) stalled by a drug...
超分子 | 名称: human ribosome nascent chain complex (CDH1-RNC) stalled by a drug-like molecule with AA tRNA and PE tRNA タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Homo sapiens (ヒト) / 組換細胞: HeLa |
分子量 | 理論値: 4.3 MDa |
-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: 7.8 |
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グリッド | 詳細: unspecified |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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電子線 | 加速電圧: 300 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 FIELDBright-field microscopy |
撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 平均電子線量: 50.0 e/Å2 |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
-画像解析
初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
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最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 10350 |
FSC曲線 (解像度の算出) |
-原子モデル構築 1
精密化 | 空間: REAL / 温度因子: 73 |
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得られたモデル | PDB-6olf: |