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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: 7xnx | ||||||
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| タイトル | High resolution cry-EM structure of the human 80S ribosome from SNORD127+/+ Kasumi-1 cells | ||||||
要素 |
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キーワード | RIBOSOME / rRNA ribomethylome | ||||||
| 機能・相同性 | 機能・相同性情報translation at presynapse / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / optic nerve development / regulation of translation involved in cellular response to UV / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist ...translation at presynapse / exit from mitosis / eukaryotic 80S initiation complex / negative regulation of protein neddylation / response to insecticide / optic nerve development / regulation of translation involved in cellular response to UV / negative regulation of endoplasmic reticulum unfolded protein response / oxidized pyrimidine DNA binding / response to TNF agonist / positive regulation of base-excision repair / axial mesoderm development / negative regulation of formation of translation preinitiation complex / positive regulation of respiratory burst involved in inflammatory response / regulation of G1 to G0 transition / ribosomal protein import into nucleus / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage / positive regulation of gastrulation / protein tyrosine kinase inhibitor activity / protein-DNA complex disassembly / positive regulation of endodeoxyribonuclease activity / IRE1-RACK1-PP2A complex / nucleolus organization / positive regulation of Golgi to plasma membrane protein transport / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / 90S preribosome assembly / retinal ganglion cell axon guidance / TNFR1-mediated ceramide production / negative regulation of DNA repair / negative regulation of RNA splicing / GAIT complex / positive regulation of DNA damage response, signal transduction by p53 class mediator / supercoiled DNA binding / TORC2 complex binding / neural crest cell differentiation / alpha-beta T cell differentiation / G1 to G0 transition / NF-kappaB complex / cysteine-type endopeptidase activator activity involved in apoptotic process / oxidized purine DNA binding / positive regulation of ubiquitin-protein transferase activity / negative regulation of intrinsic apoptotic signaling pathway in response to hydrogen peroxide / regulation of establishment of cell polarity / negative regulation of bicellular tight junction assembly / ubiquitin-like protein conjugating enzyme binding / middle ear morphogenesis / negative regulation of phagocytosis / rRNA modification in the nucleus and cytosol / Formation of the ternary complex, and subsequently, the 43S complex / erythrocyte homeostasis / cytoplasmic side of rough endoplasmic reticulum membrane / laminin receptor activity / negative regulation of ubiquitin protein ligase activity / protein kinase A binding / ion channel inhibitor activity / Ribosomal scanning and start codon recognition / pigmentation / homeostatic process / Translation initiation complex formation / positive regulation of mitochondrial depolarization / macrophage chemotaxis / positive regulation of T cell receptor signaling pathway / negative regulation of Wnt signaling pathway / fibroblast growth factor binding / lung morphogenesis / monocyte chemotaxis / positive regulation of natural killer cell proliferation / positive regulation of activated T cell proliferation / negative regulation of translational frameshifting / TOR signaling / Protein hydroxylation / BH3 domain binding / SARS-CoV-1 modulates host translation machinery / regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway / iron-sulfur cluster binding / regulation of cell division / cellular response to ethanol / mTORC1-mediated signalling / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / endonucleolytic cleavage to generate mature 3'-end of SSU-rRNA from (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / Eukaryotic Translation Termination / ubiquitin ligase inhibitor activity / positive regulation of GTPase activity / cellular response to actinomycin D / Response of EIF2AK4 (GCN2) to amino acid deficiency / blastocyst development / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / protein serine/threonine kinase inhibitor activity / positive regulation of signal transduction by p53 class mediator / Viral mRNA Translation / negative regulation of respiratory burst involved in inflammatory response / Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) / protein localization to nucleus / GTP hydrolysis and joining of the 60S ribosomal subunit / L13a-mediated translational silencing of Ceruloplasmin expression / positive regulation of protein binding 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: 2.7 Å | ||||||
データ登録者 | Cheng, J. / Beckmann, R. | ||||||
| 資金援助 | 1件
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引用 | ジャーナル: Cancer Discov / 年: 2023タイトル: A Dynamic rRNA Ribomethylome Drives Stemness in Acute Myeloid Leukemia. 著者: Fengbiao Zhou / Nesrine Aroua / Yi Liu / Christian Rohde / Jingdong Cheng / Anna-Katharina Wirth / Daria Fijalkowska / Stefanie Göllner / Michelle Lotze / Haiyang Yun / Xiaobing Yu / ...著者: Fengbiao Zhou / Nesrine Aroua / Yi Liu / Christian Rohde / Jingdong Cheng / Anna-Katharina Wirth / Daria Fijalkowska / Stefanie Göllner / Michelle Lotze / Haiyang Yun / Xiaobing Yu / Caroline Pabst / Tim Sauer / Thomas Oellerich / Hubert Serve / Christoph Röllig / Martin Bornhäuser / Christian Thiede / Claudia Baldus / Michaela Frye / Simon Raffel / Jeroen Krijgsveld / Irmela Jeremias / Roland Beckmann / Andreas Trumpp / Carsten Müller-Tidow / ![]() 要旨: The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O- ...The development and regulation of malignant self-renewal remain unresolved issues. Here, we provide biochemical, genetic, and functional evidence that dynamics in ribosomal RNA (rRNA) 2'-O-methylation regulate leukemia stem cell (LSC) activity in vivo. A comprehensive analysis of the rRNA 2'-O-methylation landscape of 94 patients with acute myeloid leukemia (AML) revealed dynamic 2'-O-methylation specifically at exterior sites of ribosomes. The rRNA 2'-O-methylation pattern is closely associated with AML development stage and LSC gene expression signature. Forced expression of the 2'-O-methyltransferase fibrillarin (FBL) induced an AML stem cell phenotype and enabled engraftment of non-LSC leukemia cells in NSG mice. Enhanced 2'-O-methylation redirected the ribosome translation program toward amino acid transporter mRNAs enriched in optimal codons and subsequently increased intracellular amino acid levels. Methylation at the single site 18S-guanosine 1447 was instrumental for LSC activity. Collectively, our work demonstrates that dynamic 2'-O-methylation at specific sites on rRNAs shifts translational preferences and controls AML LSC self-renewal. SIGNIFICANCE: We establish the complete rRNA 2'-O-methylation landscape in human AML. Plasticity of rRNA 2'-O-methylation shifts protein translation toward an LSC phenotype. This dynamic process ...SIGNIFICANCE: We establish the complete rRNA 2'-O-methylation landscape in human AML. Plasticity of rRNA 2'-O-methylation shifts protein translation toward an LSC phenotype. This dynamic process constitutes a novel concept of how cancers reprogram cell fate and function. This article is highlighted in the In This Issue feature, p. 247. | ||||||
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構造の表示
| 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 | 7xnx.cif.gz | 4.8 MB | 表示 | PDBx/mmCIF形式 |
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| PDB形式 | pdb7xnx.ent.gz | 表示 | PDB形式 | |
| PDBx/mmJSON形式 | 7xnx.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 | 7xnx_validation.pdf.gz | 1.9 MB | 表示 | wwPDB検証レポート |
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| 文書・詳細版 | 7xnx_full_validation.pdf.gz | 2.1 MB | 表示 | |
| XML形式データ | 7xnx_validation.xml.gz | 367.6 KB | 表示 | |
| CIF形式データ | 7xnx_validation.cif.gz | 629.7 KB | 表示 | |
| アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/xn/7xnx ftp://data.pdbj.org/pub/pdb/validation_reports/xn/7xnx | HTTPS FTP |
-関連構造データ
| 関連構造データ | ![]() 33329MC ![]() 7xnyC 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 | 類似検索 - 機能・相同性 F&H 検索 |
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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
-RNA鎖 , 5種, 5分子 L1L2L3S2CC
| #1: RNA鎖 | 分子量: 1641246.125 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
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| #2: 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) |
| #3: RNA鎖 | 分子量: 50477.867 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
| #45: RNA鎖 | 分子量: 603637.312 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: 24004.262 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
+60S ribosomal protein ... , 39種, 40分子 LALBLCLDLELFLGLHLJLLLMLNLOLPLQLRLSLTLULVLWLXLYLZLaLbLcLdLeLf...
-タンパク質 , 4種, 5分子 LILmSgSfCE
| #12: タンパク質 | 分子量: 24630.061 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: X5D2T3 |
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| #40: タンパク質 | 分子量: 14758.394 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P62987 |
| #66: タンパク質 | 分子量: 35115.652 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) / 参照: UniProt: P63244 |
| #78: タンパク質 | 分子量: 15702.628 Da / 分子数: 2 / 由来タイプ: 天然 / 由来: (天然) Homo sapiens (ヒト) |
+40S ribosomal protein ... , 31種, 31分子 SASBSDSESFSHSISKSLSPSQSRSSSTSUSVSXSaScSdSCSGSJSMSNSOSWSYSZSbSe
-非ポリマー , 4種, 1278分子 






| #80: 化合物 | ChemComp-MG / #81: 化合物 | ChemComp-K / #82: 化合物 | ChemComp-ZN / #83: 水 | ChemComp-HOH / | |
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-詳細
| 研究の焦点であるリガンドがあるか | N |
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| Has protein modification | Y |
-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: ribosome / タイプ: COMPLEX / Entity ID: #1-#79 / 由来: NATURAL |
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| 由来(天然) | 生物種: Homo sapiens (ヒト) |
| 緩衝液 | pH: 7.4 |
| 試料 | 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES |
| 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: TUNGSTEN HAIRPIN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
| 電子レンズ | モード: BRIGHT FIELD / 最大 デフォーカス(公称値): 2500 nm / 最小 デフォーカス(公称値): 800 nm |
| 撮影 | 電子線照射量: 44 e/Å2 / 検出モード: COUNTING 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 | 詳細: Relion / タイプ: NONE |
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| 3次元再構成 | 解像度: 2.7 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 49713 / 対称性のタイプ: POINT |
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万見について




Homo sapiens (ヒト)
引用



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microscopy
