+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6olz | ||||||
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タイトル | Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like molecule 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 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 / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / eukaryotic 80S initiation complex / response to TNF agonist / very-low-density lipoprotein particle receptor binding / positive regulation of base-excision repair / negative regulation of protein neddylation / protein tyrosine kinase inhibitor activity / embryonic brain development / positive regulation of respiratory burst involved in inflammatory response / translation at presynapse / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / axial mesoderm development / nucleolus organization / ribosomal protein import into nucleus / negative regulation of formation of translation preinitiation complex / negative regulation of low-density lipoprotein receptor activity / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / 90S preribosome assembly / TNFR1-mediated ceramide production / negative regulation of receptor internalization / endolysosome membrane / negative regulation of RNA splicing / negative regulation of DNA repair / TORC2 complex binding / regulation of signaling receptor activity / sodium channel inhibitor activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / oxidized purine DNA binding / supercoiled DNA binding / GAIT complex / neural crest cell differentiation / NF-kappaB complex / middle ear morphogenesis / ubiquitin-like protein conjugating enzyme binding / regulation of establishment of cell polarity / negative regulation of phagocytosis / positive regulation of ubiquitin-protein transferase activity / Formation of the ternary complex, and subsequently, the 43S complex / rRNA modification in the nucleus and cytosol / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / A band / laminin receptor activity / alpha-beta T cell differentiation / regulation of G1 to G0 transition / exit from mitosis / lysosomal transport / protein kinase A binding / 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 / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / optic nerve development / Translation initiation complex formation / pigmentation / low-density lipoprotein particle receptor binding / positive regulation of mitochondrial depolarization / response to aldosterone / mammalian oogenesis stage / retinal ganglion cell axon guidance / triglyceride metabolic process / G1 to G0 transition / homeostatic process / activation-induced cell death of T cells / negative regulation of Wnt signaling pathway / lung morphogenesis / positive regulation of T cell receptor signaling pathway / fibroblast growth factor binding / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / COPII-coated ER to Golgi transport vesicle / regulation of cell division / Protein hydroxylation / negative regulation of peptidyl-serine phosphorylation 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: 3.9 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. | ||||||
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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6olz.cif.gz | 4.6 MB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6olz.ent.gz | 表示 | PDB形式 | |
PDBx/mmJSON形式 | 6olz.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
文書・要旨 | 6olz_validation.pdf.gz | 2.2 MB | 表示 | wwPDB検証レポート |
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文書・詳細版 | 6olz_full_validation.pdf.gz | 2.4 MB | 表示 | |
XML形式データ | 6olz_validation.xml.gz | 367.1 KB | 表示 | |
CIF形式データ | 6olz_validation.cif.gz | 623.1 KB | 表示 | |
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/ol/6olz ftp://data.pdbj.org/pub/pdb/validation_reports/ol/6olz | HTTPS FTP |
-関連構造データ
関連構造データ | 0598MC 0526C 0596C 0597C 0599C 0600C 0601C 6oleC 6olfC 6olgC 6oliC 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 (文献) |
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類似構造データ |
-リンク
-集合体
登録構造単位 |
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1 |
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-要素
+60S ribosomal protein ... , 42種, 42分子 AAABACADAEAFAGAHAIAJALAMANAOAPAQARASATAUAVAWAXAYAZAaAbAcAdAe...
+40S ribosomal protein ... , 31種, 31分子 BABBBCBDBEBFBGBHBIBJBKBLBMBNBOBPBQBRBSBTBUBVBWBXBYBZBaBbBcBdBe
-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) |
#48: RNA鎖 | 分子量: 1180347.500 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
#49: 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) |
#80: 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) |
#81: 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 BfBg
#78: タンパク質 | 分子量: 8645.277 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62979 |
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#79: 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
#82: 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 |
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-非ポリマー , 3種, 332分子
#83: 化合物 | ChemComp-MG / #84: 化合物 | ChemComp-ZN / #85: 化合物 | ChemComp-MVM / | |
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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 |
-試料調製
構成要素 | 名称: Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like molecule with PP tRNA タイプ: RIBOSOME / Entity ID: #1-#82 / 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 |
-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) |
-解析
CTF補正 | タイプ: NONE |
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3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 7214 / 対称性のタイプ: POINT |