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基本情報
登録情報 | データベース: EMDB / ID: EMD-0598 | |||||||||
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タイトル | Structure of a drug-like molecule stalled ribosome nascent chain complex (PCSK9_RNC) in non-rotated state with PP tRNA | |||||||||
![]() | PF846 stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP tRNA. Map is sharpened. | |||||||||
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機能・相同性 | ![]() negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / PCSK9-LDLR complex / very-low-density lipoprotein particle binding / negative regulation of receptor recycling / PCSK9-AnxA2 complex / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding ...negative regulation of low-density lipoprotein particle receptor binding / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / low-density lipoprotein particle receptor catabolic process / extrinsic component of external side of plasma membrane / PCSK9-LDLR complex / very-low-density lipoprotein particle binding / negative regulation of receptor recycling / PCSK9-AnxA2 complex / negative regulation of sodium ion transmembrane transporter activity / apolipoprotein receptor binding / negative regulation of low-density lipoprotein particle clearance / low-density lipoprotein particle binding / signaling receptor inhibitor activity / LDL clearance / positive regulation of low-density lipoprotein particle receptor catabolic process / lipoprotein metabolic process / eukaryotic 80S initiation complex / very-low-density lipoprotein particle receptor binding / negative regulation of protein neddylation / embryonic brain development / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / translation at presynapse / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein tyrosine kinase inhibitor activity / axial mesoderm development / positive regulation of respiratory burst involved in inflammatory response / ribosomal protein import into nucleus / negative regulation of low-density lipoprotein receptor activity / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / negative regulation of formation of translation preinitiation complex / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / nucleolus organization / IRE1-RACK1-PP2A complex / 90S preribosome assembly / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / TNFR1-mediated ceramide production / negative regulation of receptor internalization / endolysosome membrane / negative regulation of DNA repair / negative regulation of RNA splicing / TORC2 complex binding / regulation of signaling receptor activity / sodium channel inhibitor activity / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / neural crest cell differentiation / middle ear morphogenesis / NF-kappaB complex / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / A band / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / alpha-beta T cell differentiation / regulation of G1 to G0 transition / laminin receptor activity / lysosomal transport / 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 / protein kinase A binding / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / optic nerve development / negative regulation of ubiquitin protein ligase activity / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / triglyceride metabolic process / low-density lipoprotein particle receptor binding / response to aldosterone / Translation initiation complex formation / pigmentation / retinal ganglion cell axon guidance / positive regulation of mitochondrial depolarization / mammalian oogenesis stage / G1 to G0 transition / homeostatic process / activation-induced cell death of T cells / macrophage chemotaxis / negative regulation of Wnt signaling pathway / lung morphogenesis / positive regulation of T cell receptor signaling pathway / COPII-coated ER to Golgi transport vesicle / fibroblast growth factor binding / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / regulation of cell division / Protein hydroxylation / monocyte chemotaxis 類似検索 - 分子機能 | |||||||||
生物種 | ![]() | |||||||||
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 | |||||||||
![]() | Li W / Cate JHD | |||||||||
資金援助 | ![]()
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![]() | ![]() 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 |
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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 | ![]() | 229 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 17.2 KB 17.2 KB | 表示 表示 | ![]() |
FSC (解像度算出) | ![]() | 14.2 KB | 表示 | ![]() |
画像 | ![]() | 163.5 KB | ||
その他 | ![]() ![]() ![]() | 193.1 MB 193.8 MB 193.8 MB | ||
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
関連構造データ | ![]() 6olzMC ![]() 0526C ![]() 0596C ![]() 0597C ![]() 0599C ![]() 0600C ![]() 0601C ![]() 6oleC ![]() 6olfC ![]() 6olgC ![]() 6oliC ![]() 6om0C ![]() 6om7C C: 同じ文献を引用 ( 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 |
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リンク
EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | PF846 stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP tRNA. Map is sharpened. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.22 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 (PCSK9-RNC)...
ファイル | emd_0598_additional.map | ||||||||||||
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注釈 | PF846 stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP 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_0598_half_map_1.map | ||||||||||||
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注釈 | Half map of PF846 stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP 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_0598_half_map_2.map | ||||||||||||
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注釈 | Half map of PF846 stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP tRNA. | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
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試料の構成要素
-全体 : Drug-like molecule stalled human ribosome nascent chain complex (...
全体 | 名称: Drug-like molecule stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP tRNA |
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要素 |
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-超分子 #1: Drug-like molecule stalled human ribosome nascent chain complex (...
超分子 | 名称: Drug-like molecule stalled human ribosome nascent chain complex (PCSK9-RNC) in non-rotated state with PP tRNA タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all |
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由来(天然) | 生物種: ![]() |
組換発現 | 生物種: ![]() |
分子量 | 理論値: 4.3 MDa |
-分子 #1: human ribosome with nascent chain
分子 | 名称: human ribosome with nascent chain / タイプ: rna / ID: 1 詳細: Nascent chain sequence including CDH1 domain V and PCSK9 1-35 |
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由来(天然) | 生物種: ![]() |
配列 | 文字列: SDVNDNAPIP EPRTIFFCER NPKPQVINII DADLPPNTSP FTAELTHGAS ANWTIQYNDP TQESIILKPK MALEVGDYKI NLKLMDNQNK DQVTTLEVSV CDCEGAAGVC RKAQPVEAGL QIPAILGILG MGTVSSRRS WWPLPLLLLL LLLLGPAGAR AQEDED |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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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: 4 K |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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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 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
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: 7214 |
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初期 角度割当 | タイプ: ANGULAR RECONSTITUTION |
最終 角度割当 | タイプ: ANGULAR RECONSTITUTION |
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: 80 |
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得られたモデル | ![]() PDB-6olz: |