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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) | ||||||
要素 |
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キーワード | RIBOSOME / selective stalling / drug-like molecule / human ribosome nascent chain complex | ||||||
| 機能・相同性 | 機能・相同性情報response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / gamma-catenin binding / desmosome / Regulation of CDH1 mRNA translation by microRNAs / cell adhesion mediator activity / negative regulation of axon extension ...response to heparin / desmosome assembly / response to Gram-positive bacterium / pituitary gland development / Regulation of MITF-M-dependent genes involved in extracellular matrix, focal adhesion and epithelial-to-mesenchymal transition / gamma-catenin binding / desmosome / Regulation of CDH1 mRNA translation by microRNAs / cell adhesion mediator activity / negative regulation of axon extension / cellular response to indole-3-methanol / calcium-dependent cell-cell adhesion / regulation of protein catabolic process at postsynapse, modulating synaptic transmission / flotillin complex / Developmental Lineage of Mammary Stem Cells / Formation of definitive endoderm / cell-cell adhesion mediated by cadherin / adherens junction organization / embryonic brain development / Apoptotic cleavage of cell adhesion proteins / catenin complex / translation at presynapse / exit from mitosis / optic nerve development / Regulation of CDH1 Function / response to insecticide / cell-cell junction assembly / regulation of translation involved in cellular response to UV / eukaryotic 80S initiation complex / Adherens junctions interactions / 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 / 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 / GTPase activating protein binding / 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 / TNFR1-mediated ceramide production / positive regulation of DNA damage response, signal transduction by p53 class mediator / GAIT complex / negative regulation of RNA splicing / ankyrin binding / negative regulation of cell-cell adhesion / TORC2 complex binding / neural crest cell differentiation / supercoiled DNA binding / NF-kappaB complex / negative regulation of DNA repair / G1 to G0 transition / cytoplasmic translational initiation / cellular response to lithium ion / 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 / Regulation of CDH1 posttranslational processing and trafficking to plasma membrane / rRNA modification in the nucleus and cytosol / apical junction complex / 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 / homophilic cell-cell adhesion / Translation initiation complex formation / homeostatic process / pigmentation / positive regulation of mitochondrial depolarization / Developmental Lineage of Mammary Gland Myoepithelial Cells / macrophage chemotaxis / lung morphogenesis / negative regulation of Wnt signaling pathway / positive regulation of natural killer cell proliferation / fibroblast growth factor binding / monocyte chemotaxis / BH3 domain binding / Protein hydroxylation / negative regulation of translational frameshifting 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: 3.4 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 |
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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 | 6olg.cif.gz | 4.7 MB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb6olg.ent.gz | 表示 | PDB形式 | |
| PDBx/mmJSON形式 | 6olg.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/ol/6olg ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6olg | HTTPS FTP |
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-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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| 1 |
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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) Homo sapiens (ヒト) |
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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) Homo sapiens (ヒト) |
| #51: RNA鎖 | 分子量: 1170164.875 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #52: RNA鎖 | 分子量: 551108.188 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #83: RNA鎖 | 分子量: 24485.539 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #84: RNA鎖 | 分子量: 4853.695 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
-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) Homo sapiens (ヒト) / 参照: UniProt: P05388 |
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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) Homo sapiens (ヒト) / 参照: UniProt: P63244 |
-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) Homo sapiens (ヒト) / 参照: UniProt: P12830 |
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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: 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: 3.4 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 |
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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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