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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: 8a3d | ||||||
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タイトル | Human mature large subunit of the ribosome with eIF6 and homoharringtonine bound | ||||||
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![]() | TRANSLATION / Ribosome / human / rna modifications / water / magnesium / potassium / homoharringtonine | ||||||
機能・相同性 | ![]() lamin filament / regulation of fatty acid biosynthetic process / regulation of megakaryocyte differentiation / miRNA-mediated post-transcriptional gene silencing / miRNA-mediated gene silencing by inhibition of translation / embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / regulation of G1 to G0 transition / axial mesoderm development ...lamin filament / regulation of fatty acid biosynthetic process / regulation of megakaryocyte differentiation / miRNA-mediated post-transcriptional gene silencing / miRNA-mediated gene silencing by inhibition of translation / embryonic brain development / eukaryotic 80S initiation complex / negative regulation of protein neddylation / regulation of G1 to G0 transition / axial mesoderm development / negative regulation of formation of translation preinitiation complex / ribosomal protein import into nucleus / regulation of translation involved in cellular response to UV / protein-DNA complex disassembly / 90S preribosome assembly / positive regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator / GAIT complex / A band / positive regulation of DNA damage response, signal transduction by p53 class mediator / TORC2 complex binding / alpha-beta T cell differentiation / G1 to G0 transition / regulation of glycolytic process / exit from mitosis / translation at presynapse / regulation of reactive oxygen species metabolic process / middle ear morphogenesis / optic nerve development / cytoplasmic side of rough endoplasmic reticulum membrane / maturation of 5.8S rRNA / retinal ganglion cell axon guidance / negative regulation of ubiquitin protein ligase activity / homeostatic process / response to aldosterone / macrophage chemotaxis / lung morphogenesis / ribosomal large subunit binding / Protein hydroxylation / Peptide chain elongation / Selenocysteine synthesis / Formation of a pool of free 40S subunits / ubiquitin ligase inhibitor activity / Eukaryotic Translation Termination / positive regulation of signal transduction by p53 class mediator / blastocyst development / Response of EIF2AK4 (GCN2) to amino acid deficiency / SRP-dependent cotranslational protein targeting to membrane / negative regulation of ubiquitin-dependent protein catabolic process / cellular response to actinomycin D / Viral mRNA Translation / 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 / Major pathway of rRNA processing in the nucleolus and cytosol / ribosomal subunit export from nucleus / protein targeting / protein-RNA complex assembly / Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) / maturation of LSU-rRNA / rough endoplasmic reticulum / translation regulator activity / cytosolic ribosome / MDM2/MDM4 family protein binding / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / translation initiation factor activity / embryo implantation / cellular response to interleukin-4 / ossification / innate immune response in mucosa / assembly of large subunit precursor of preribosome / maturation of LSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) / ribosomal large subunit biogenesis / cytosolic ribosome assembly / regulation of signal transduction by p53 class mediator / positive regulation of translation / mRNA 3'-UTR binding / skeletal system development / DNA damage response, signal transduction by p53 class mediator / response to insulin / sensory perception of sound / transcription coactivator binding / cellular response to gamma radiation / bone development / mRNA 5'-UTR binding / cellular response to type II interferon / Regulation of expression of SLITs and ROBOs / cytoplasmic ribonucleoprotein granule / antimicrobial humoral immune response mediated by antimicrobial peptide / positive regulation of protein binding / rRNA processing / cellular response to UV / antibacterial humoral response / large ribosomal subunit / presynapse / regulation of translation / heparin binding / ribosome binding / cell body / retina development in camera-type eye 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: 1.67 Å | ||||||
![]() | Faille, A. / Warren, A.J. / Dent, K.C. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: The chemical landscape of the human ribosome at 1.67 Å resolution. 著者: Alexandre Faille / Kyle C Dent / Simone Pellegrino / Pekka Jaako / Alan J Warren 要旨: The ability of ribosomes to translate the genetic code into protein requires a finely tuned ion and solvent ecosystem. However, the lack of high-resolution structures has precluded accurate ...The ability of ribosomes to translate the genetic code into protein requires a finely tuned ion and solvent ecosystem. However, the lack of high-resolution structures has precluded accurate positioning of all the functional elements of the ribosome and limited our understanding of the specific role of ribosomal RNA chemical modifications in modulating ribosome function in health and disease. Here, using a new sample preparation methodology based on functionalised pristine graphene-coated grids, we solve the cryo-EM structure of the human large ribosomal subunit to a resolution of 1.67 Å. The accurate assignment of water molecules, magnesium and potassium ions in our model highlights the fundamental biological role of ribosomal RNA methylation in harnessing unconventional carbon-oxygen hydrogen bonds to establish chemical interactions with the environment and fine-tune the functional interplay with tRNA. In addition, the structures of three translational inhibitors bound to the human large ribosomal subunit at better than 2 Å resolution provide mechanistic insights into how three key druggable pockets of the ribosome are targeted and illustrate the potential of this methodology to accelerate high-throughput structure-based design of anti-cancer therapeutics. | ||||||
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構造の表示
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 | ![]() | 3.7 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 | ![]() | 1.6 MB | 表示 | ![]() |
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文書・詳細版 | ![]() | 1.8 MB | 表示 | |
XML形式データ | ![]() | 239.8 KB | 表示 | |
CIF形式データ | ![]() | 459.9 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 | ![]() 15113MC 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 ![]() |
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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 , 3種, 3分子 ABC
#1: RNA鎖 | 分子量: 1640812.500 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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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) ![]() |
#3: RNA鎖 | 分子量: 50463.840 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
+60S ribosomal protein ... , 39種, 39分子 DEFGHmnopqrslIJKLMNOPQRSTUVWXY...
-タンパク質 , 3種, 3分子 bgh
#36: タンパク質 | 分子量: 21730.748 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
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#41: タンパク質 | 分子量: 11470.713 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
#45: タンパク質 | 分子量: 26620.010 Da / 分子数: 1 / 由来タイプ: 天然 / 由来: (天然) ![]() |
-非ポリマー , 8種, 12367分子 














#46: 化合物 | ChemComp-MG / #47: 化合物 | ChemComp-K / #48: 化合物 | #49: 化合物 | ChemComp-HMT / ( | #50: 化合物 | ChemComp-SPM / | #51: 化合物 | ChemComp-EPE / | #52: 化合物 | ChemComp-ZN / #53: 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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-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 mature large subunit of the ribosome with eIF6 bound タイプ: RIBOSOME / Entity ID: #1-#45 / 由来: NATURAL | |||||||||||||||||||||||||
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分子量 | 実験値: NO | |||||||||||||||||||||||||
由来(天然) | 生物種: ![]() | |||||||||||||||||||||||||
緩衝液 | pH: 7.5 | |||||||||||||||||||||||||
緩衝液成分 |
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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: Grid was functionalised with 1-pyrenemethylamine. See methods section in published article. グリッドの材料: COPPER / グリッドのサイズ: 300 divisions/in. / グリッドのタイプ: Quantifoil R2/2 | |||||||||||||||||||||||||
急速凍結 | 装置: FEI VITROBOT MARK IV / 凍結剤: ETHANE / 湿度: 100 % / 凍結前の試料温度: 277 K / 詳細: 30 seconds 'wait' time |
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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 / 倍率(公称値): 105000 X / 最大 デフォーカス(公称値): 1800 nm / 最小 デフォーカス(公称値): 1000 nm / Cs: 2.7 mm / C2レンズ絞り径: 50 µm / アライメント法: COMA FREE |
試料ホルダ | 凍結剤: NITROGEN 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 2.2 sec. / 電子線照射量: 51 e/Å2 フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 9973 |
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解析
ソフトウェア | 名称: REFMAC / バージョン: 5.8.0267 / 分類: 精密化 | ||||||||||||||||||||||||||||||||||||
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EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
粒子像の選択 | 選択した粒子像数: 1147785 | ||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 1.67 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 1088709 / クラス平均像の数: 1 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | B value: 40 / プロトコル: AB INITIO MODEL / 空間: REAL | ||||||||||||||||||||||||||||||||||||
原子モデル構築 | PDB-ID: 6EK0![]() 6ek0 Accession code: 6EK0 / Source name: PDB / タイプ: experimental model | ||||||||||||||||||||||||||||||||||||
精密化 | 解像度: 1.67→270.25 Å / Cor.coef. Fo:Fc: 0.688
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原子変位パラメータ | Biso mean: 35.442 Å2 | ||||||||||||||||||||||||||||||||||||
LS精密化 シェル | 最高解像度: 1.67 Å /
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