+
データを開く
-
基本情報
登録情報 | データベース: PDB / ID: 6om7 | ||||||
---|---|---|---|---|---|---|---|
タイトル | Human ribosome nascent chain complex (PCSK9-RNC) stalled by a drug-like small molecule with AA and PE tRNAs | ||||||
![]() |
| ||||||
![]() | RIBOSOME / selective stalling / drug-like small molecule / human ribosome nascent chain complex | ||||||
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 / positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis / negative regulation of endoplasmic reticulum unfolded protein response / embryonic brain development / eukaryotic 80S initiation complex / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / negative regulation of protein neddylation / protein tyrosine kinase inhibitor activity / translation at presynapse / positive regulation of respiratory burst involved in inflammatory response / axial mesoderm development / very-low-density lipoprotein particle receptor binding / 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 / negative regulation of formation of translation preinitiation complex / nucleolus organization / ribosomal protein import into nucleus / IRE1-RACK1-PP2A complex / : / positive regulation of endodeoxyribonuclease activity / positive regulation of Golgi to plasma membrane protein transport / 90S preribosome assembly / negative regulation of low-density lipoprotein receptor activity / TNFR1-mediated ceramide production / negative regulation of RNA splicing / negative regulation of DNA repair / negative regulation of receptor internalization / TORC2 complex binding / endolysosome membrane / regulation of signaling receptor activity / GAIT complex / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / sodium channel inhibitor activity / oxidized purine DNA binding / supercoiled DNA binding / 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 / cytoplasmic side of rough endoplasmic reticulum membrane / erythrocyte homeostasis / A band / laminin receptor activity / regulation of G1 to G0 transition / alpha-beta T cell differentiation / 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 kinase A binding / protein-DNA complex disassembly / lysosomal transport / positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator / Translation initiation complex formation / optic nerve development / Ribosomal scanning and start codon recognition / negative regulation of ubiquitin protein ligase activity / ion channel inhibitor activity / pigmentation / mammalian oogenesis stage / positive regulation of mitochondrial depolarization / response to aldosterone / retinal ganglion cell axon guidance / low-density lipoprotein particle receptor binding / G1 to G0 transition / triglyceride metabolic process / homeostatic process / activation-induced cell death of T cells / lung morphogenesis / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / positive regulation of T cell receptor signaling pathway / positive regulation of activated T cell proliferation / iron-sulfur cluster binding / Protein hydroxylation / COPII-coated ER to Golgi transport vesicle / regulation of cell division / negative regulation of peptidyl-serine phosphorylation 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: 3.7 Å | ||||||
![]() | Li, W. / Cate, J.H.D. | ||||||
資金援助 | ![]()
| ||||||
![]() | ![]() 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 |
|
-
構造の表示
ムービー |
![]() |
---|---|
構造ビューア | 分子: ![]() ![]() |
-
ダウンロードとリンク
-
ダウンロード
PDBx/mmCIF形式 | ![]() | 4.6 MB | 表示 | ![]() |
---|---|---|---|---|
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 | ![]() |
---|---|---|---|---|
文書・詳細版 | ![]() | 2.5 MB | 表示 | |
XML形式データ | ![]() | 377 KB | 表示 | |
CIF形式データ | ![]() | 628.7 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 | ![]() 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 ( |
---|---|
類似構造データ |
-
リンク
-
集合体
登録構造単位 | ![]()
|
---|---|
1 |
|
-
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) ![]() |
---|---|
#38: RNA鎖 | 分子量: 50449.812 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#39: RNA鎖 | 分子量: 38998.078 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#79: RNA鎖 | 分子量: 1168718.500 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#80: RNA鎖 | 分子量: 24436.508 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#81: RNA鎖 | 分子量: 3193.932 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#82: RNA鎖 | 分子量: 24414.451 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+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) ![]() |
---|---|
#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) ![]() |
-非ポリマー , 4種, 52分子 ![](data/chem/img/ZN.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/MVM.gif)
![](data/chem/img/HOH.gif)
![](data/chem/img/MG.gif)
![](data/chem/img/MVM.gif)
![](data/chem/img/HOH.gif)
#84: 化合物 | ChemComp-ZN / #85: 化合物 | ChemComp-MG / #86: 化合物 | ChemComp-MVM / | #87: 水 | ChemComp-HOH / | |
---|
-実験情報
-実験
実験 | 手法: 電子顕微鏡法 |
---|---|
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 stalled by a drug-like small molecule (PCSK9_RNC) withAA and PP tRNAs タイプ: RIBOSOME / Entity ID: #1-#83 / 由来: NATURAL |
---|---|
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 |
-
電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
---|---|
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) |
-
解析
CTF補正 | タイプ: NONE |
---|---|
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 |