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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: 6olg | ||||||
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タイトル | Human ribosome nascent chain complex stalled by a drug-like small molecule (CDH1_RNC with PP tRNA) | ||||||
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![]() | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
機能・相同性 | ![]() response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / gamma-catenin binding / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / negative regulation of axon extension / desmosome / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules ...response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / gamma-catenin binding / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / negative regulation of axon extension / desmosome / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules / flotillin complex / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / cell-cell adhesion mediated by cadherin / Formation of definitive endoderm / embryonic brain development / catenin complex / eukaryotic 80S initiation complex / Apoptotic cleavage of cell adhesion proteins / negative regulation of protein neddylation / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of formation of translation preinitiation complex / regulation of G1 to G0 transition / axial mesoderm development / positive regulation of respiratory burst involved in inflammatory response / ribosomal protein import into nucleus / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / adherens junction organization / 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 / GTPase activating protein binding / positive regulation of gastrulation / nucleolus organization / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / protein tyrosine kinase inhibitor activity / protein-DNA complex disassembly / cell-cell junction assembly / 90S preribosome assembly / Adherens junctions interactions / IRE1-RACK1-PP2A complex / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / translation at postsynapse / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / mammalian oogenesis stage / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / A band / supercoiled DNA binding / activation-induced cell death of T cells / TORC2 complex binding / neural crest cell differentiation / alpha-beta T cell differentiation / G1 to G0 transition / NF-kappaB complex / oxidized purine DNA binding / middle ear morphogenesis / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / cysteine-type endopeptidase activator activity involved in apoptotic process / exit from mitosis / ankyrin binding / negative regulation of peptidyl-serine phosphorylation / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / translation at presynapse / positive regulation of ubiquitin-protein transferase activity / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / negative regulation of phagocytosis / erythrocyte homeostasis / optic nerve development / negative regulation of cell-cell adhesion / cytoplasmic side of rough endoplasmic reticulum membrane / apical junction complex / laminin receptor activity / protein kinase A binding / retinal ganglion cell axon guidance / negative regulation of ubiquitin protein ligase activity / pigmentation / cellular response to lithium ion / Ribosomal scanning and start codon recognition / ion channel inhibitor activity / response to aldosterone / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / positive regulation of T cell receptor signaling pathway / macrophage chemotaxis / homophilic cell adhesion via plasma membrane adhesion molecules / positive regulation of activated T cell proliferation / fibroblast growth factor binding / negative regulation of Wnt signaling pathway / lung morphogenesis / monocyte chemotaxis / negative regulation of translational frameshifting / Protein hydroxylation 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
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: 3.4 Å | ||||||
![]() | Li, W. / Cate, J.H.D. | ||||||
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 | 分子: ![]() ![]() |
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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 | ![]() | 4.7 MB | 表示 | ![]() |
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PDB形式 | ![]() | 表示 | ![]() | |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 2.3 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 2.5 MB | 表示 | |
XML形式データ | ![]() | 371.4 KB | 表示 | |
CIF形式データ | ![]() | 628.5 KB | 表示 | |
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 | ![]() 0601MC ![]() 0526C ![]() 0596C ![]() 0597C ![]() 0598C ![]() 0599C ![]() 0600C ![]() 6oleC ![]() 6olfC ![]() 6oliC ![]() 6olzC ![]() 6om0C ![]() 6om7C 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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要素
+60S ribosomal protein ... , 44種, 44分子 AAABACADAEAFAGAHAIAJALAMANAOAPAQARASATAUAVAWAXAYAZAaAbAcAdAe...
+40S ribosomal protein ... , 32種, 32分子 BABBBCBDBEBFBGBHBIBJBKBLBMBNBOBPBQBRBSBTBUBVBWBXBYBZBaBbBcBdBeBf
-RNA鎖 , 6種, 6分子 A3A4A2B1BvBx
#7: RNA鎖 | 分子量: 50449.812 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#8: RNA鎖 | 分子量: 38385.750 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#51: RNA鎖 | 分子量: 1170164.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#52: RNA鎖 | 分子量: 551108.188 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#83: RNA鎖 | 分子量: 24485.539 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#84: RNA鎖 | 分子量: 4853.695 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-タンパク質 , 2種, 2分子 AKBg
#16: タンパク質 | 分子量: 12505.798 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#82: タンパク質 | 分子量: 34726.164 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-タンパク質・ペプチド , 1種, 1分子 A
#85: タンパク質・ペプチド | 分子量: 4040.040 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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-非ポリマー , 3種, 332分子 




#86: 化合物 | ChemComp-MG / #87: 化合物 | ChemComp-ZN / #88: 化合物 | ChemComp-MVM / | |
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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 (CDH1_RNC with PP tRNA) タイプ: RIBOSOME / Entity ID: #1-#85 / 由来: NATURAL |
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由来(天然) | 生物種: ![]() |
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: ![]() |
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: 3.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 16594 / 対称性のタイプ: POINT |