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データを開く
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基本情報
| 登録情報 | データベース: PDB / ID: 6om7 | ||||||
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| タイトル | Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like small molecule with AA and PE tRNAs | ||||||
要素 |
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キーワード | RIBOSOME / selective stalling / drug-like small molecule / human ribosome nascent chain complex | ||||||
| 機能・相同性 | 機能・相同性情報low-density lipoprotein particle receptor catabolic process / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / extrinsic component of external side of plasma membrane / negative regulation of sodium ion import across plasma membrane / PCSK9-LDLR complex / PCSK9-AnxA2 complex / negative regulation of receptor recycling / apolipoprotein receptor binding / very-low-density lipoprotein particle binding / positive regulation of low-density lipoprotein particle receptor catabolic process ...low-density lipoprotein particle receptor catabolic process / negative regulation of receptor-mediated endocytosis involved in cholesterol transport / extrinsic component of external side of plasma membrane / negative regulation of sodium ion import across plasma membrane / PCSK9-LDLR complex / PCSK9-AnxA2 complex / negative regulation of receptor recycling / apolipoprotein receptor binding / very-low-density lipoprotein particle binding / positive regulation of low-density lipoprotein particle receptor catabolic process / low-density lipoprotein particle binding / LDL clearance / lipoprotein metabolic process / very-low-density lipoprotein particle receptor binding / transporter inhibitor activity / signaling receptor inhibitor activity / embryonic brain development / negative regulation of receptor internalization / translation at presynapse / COPII-coated ER to Golgi transport vesicle / exit from mitosis / sodium channel inhibitor activity / optic nerve development / response to insecticide / endolysosome membrane / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / negative regulation of formation of translation preinitiation complex / axial mesoderm development / negative regulation of endoplasmic reticulum unfolded protein response / ribosomal protein import into nucleus / regulation of G1 to G0 transition / retinal ganglion cell axon guidance / negative regulation of low-density lipoprotein particle clearance / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / protein-DNA complex disassembly / positive regulation of ubiquitin-protein transferase activity / positive regulation of respiratory burst involved in inflammatory response / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / positive regulation of gastrulation / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / protein tyrosine kinase inhibitor activity / 90S preribosome assembly / IRE1-RACK1-PP2A complex / positive regulation of Golgi to plasma membrane protein transport / nucleolus organization / alpha-beta T cell differentiation / positive regulation of DNA-templated transcription initiation / lysosomal transport / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / triglyceride metabolic process / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / low-density lipoprotein particle receptor binding / G1 to G0 transition / cytoplasmic translational initiation / oxidized purine DNA binding / cysteine-type endopeptidase activator activity involved in apoptotic process / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / rRNA modification in the nucleus and cytosol / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / protein kinase A binding / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / laminin receptor activity / Translation initiation complex formation / homeostatic process / pigmentation / positive regulation of mitochondrial depolarization / protein autoprocessing / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / 加水分解酵素; プロテアーゼ; ペプチド結合加水分解酵素; セリンエンドペプチターゼ / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of receptor internalization / TOR signaling / positive regulation of GTPase activity 類似検索 - 分子機能 | ||||||
| 生物種 | 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: 3.7 Å | ||||||
データ登録者 | Li, W. / Cate, J.H.D. | ||||||
| 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. | ||||||
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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 | 分子: Molmil Jmol/JSmol |
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ダウンロードとリンク
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ダウンロード
| PDBx/mmCIF形式 | 6om7.cif.gz | 4.7 MB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb6om7.ent.gz | 表示 | PDB形式 | |
| PDBx/mmJSON形式 | 6om7.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
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/om/6om7 ftp://data.pdbj.org/pub/pdb/validation_reports/om/6om7 | HTTPS FTP |
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-関連構造データ
| 関連構造データ | ![]() 0597MC ![]() 0526C ![]() 0596C ![]() 0598C ![]() 0599C ![]() 0600C ![]() 0601C ![]() 6oleC ![]() 6olfC ![]() 6olgC ![]() 6oliC ![]() 6olzC ![]() 6om0C 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 ( |
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| 類似構造データ |
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リンク
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集合体
| 登録構造単位 | ![]()
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| 1 |
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要素
-RNA鎖 , 7種, 7分子 S2DEtvwu
| #1: RNA鎖 | 分子量: 553505.062 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
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| #38: RNA鎖 | 分子量: 50449.812 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #39: RNA鎖 | 分子量: 38998.078 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #79: RNA鎖 | 分子量: 1168718.500 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #80: RNA鎖 | 分子量: 24436.508 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #81: RNA鎖 | 分子量: 3193.932 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #82: RNA鎖 | 分子量: 24414.451 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
+40S ribosomal protein ... , 32種, 32分子 SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSeSf
+60S ribosomal protein ... , 42種, 42分子 ABCFGHIJKLMNOPQRSTUVWXYZabcdef...
-タンパク質 / タンパク質・ペプチド , 2種, 2分子 Sgy
| #22: タンパク質 | 分子量: 34568.012 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P63244 |
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| #83: タンパク質・ペプチド | 分子量: 2886.409 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: Q8NBP7 |
-非ポリマー , 4種, 52分子 






| #84: 化合物 | ChemComp-ZN / #85: 化合物 | ChemComp-MG / #86: 化合物 | ChemComp-MVM / | #87: 水 | ChemComp-HOH / | |
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-詳細
| Has protein modification | Y |
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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 |
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試料調製
| 構成要素 | 名称: Human ribosome nascent chain complex stalled by a drug-like small molecule (PCSK9_RNC) withAA and PP tRNAs タイプ: RIBOSOME / Entity ID: #1-#83 / 由来: NATURAL |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 緩衝液 | pH: 7.5 |
| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
| 試料支持 | 詳細: unspecified |
| 急速凍結 | 凍結剤: ETHANE |
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電子顕微鏡撮影
| 実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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| 顕微鏡 | モデル: FEI TITAN KRIOS |
| 電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
| 電子レンズ | モード: BRIGHT FIELD |
| 撮影 | 電子線照射量: 50 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
| CTF補正 | タイプ: NONE |
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| 3次元再構成 | 解像度: 3.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 9564 / 対称性のタイプ: POINT |
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万見について




Homo sapiens (ヒト)
米国, 1件
引用
UCSF Chimera
























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