+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0652 | |||||||||
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タイトル | Structural basis of Dot1L stimulation by histone H2B lysine 120 ubiquitination. 3.5A reconstruction of Dot1L on H2BK120Ub nucleosome | |||||||||
マップデータ | Final map from cisTEM, filtered at 3.5A, unsharpened | |||||||||
試料 |
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機能・相同性 | 機能・相同性情報 histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / hypothalamus gonadotrophin-releasing hormone neuron development / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / female meiosis I / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule ...histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / hypothalamus gonadotrophin-releasing hormone neuron development / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / female meiosis I / positive regulation of protein monoubiquitination / mitochondrion transport along microtubule / fat pad development / female gonad development / histone methyltransferase activity / seminiferous tubule development / male meiosis I / positive regulation of intrinsic apoptotic signaling pathway by p53 class mediator / regulation of neuron apoptotic process / regulation of proteasomal protein catabolic process / energy homeostasis / Maturation of protein E / Maturation of protein E / ER Quality Control Compartment (ERQC) / Myoclonic epilepsy of Lafora / FLT3 signaling by CBL mutants / Prevention of phagosomal-lysosomal fusion / IRAK2 mediated activation of TAK1 complex / Alpha-protein kinase 1 signaling pathway / Glycogen synthesis / Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / Constitutive Signaling by NOTCH1 HD Domain Mutants / Regulation of FZD by ubiquitination / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / NOTCH2 Activation and Transmission of Signal to the Nucleus / APC/C:Cdc20 mediated degradation of Cyclin B / p75NTR recruits signalling complexes / Downregulation of ERBB4 signaling / telomere organization / APC-Cdc20 mediated degradation of Nek2A / TRAF6-mediated induction of TAK1 complex within TLR4 complex / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / PINK1-PRKN Mediated Mitophagy / Pexophagy / Regulation of innate immune responses to cytosolic DNA / InlA-mediated entry of Listeria monocytogenes into host cells / VLDLR internalisation and degradation / Regulation of pyruvate metabolism / Downregulation of ERBB2:ERBB3 signaling / NF-kB is activated and signals survival / Regulation of PTEN localization / NRIF signals cell death from the nucleus / Regulation of BACH1 activity / Activated NOTCH1 Transmits Signal to the Nucleus / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by REV1 / MAP3K8 (TPL2)-dependent MAPK1/3 activation / Translesion synthesis by POLK / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / neuron projection morphogenesis / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / Josephin domain DUBs / Regulation of activated PAK-2p34 by proteasome mediated degradation / InlB-mediated entry of Listeria monocytogenes into host cell / IKK complex recruitment mediated by RIP1 / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / regulation of mitochondrial membrane potential / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / DNA damage checkpoint signaling / TNFR1-induced NF-kappa-B signaling pathway / Autodegradation of Cdh1 by Cdh1:APC/C / positive regulation of protein ubiquitination / APC/C:Cdc20 mediated degradation of Securin / Asymmetric localization of PCP proteins / TCF dependent signaling in response to WNT / SCF-beta-TrCP mediated degradation of Emi1 / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / Regulation of NF-kappa B signaling / AUF1 (hnRNP D0) binds and destabilizes mRNA / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Vpu mediated degradation of CD4 / Assembly of the pre-replicative complex / Negative regulators of DDX58/IFIH1 signaling / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / NOTCH3 Activation and Transmission of Signal to the Nucleus / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.5 Å | |||||||||
データ登録者 | Valencia-Sanchez MI / De Ioannes P / Wang M / Vasilyev N / Chen R / Nudler E / Armache J-P / Armache K-J | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Mol Cell / 年: 2019 タイトル: Structural Basis of Dot1L Stimulation by Histone H2B Lysine 120 Ubiquitination. 著者: Marco Igor Valencia-Sánchez / Pablo De Ioannes / Miao Wang / Nikita Vasilyev / Ruoyu Chen / Evgeny Nudler / Jean-Paul Armache / Karim-Jean Armache / 要旨: The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of ...The essential histone H3 lysine 79 methyltransferase Dot1L regulates transcription and genomic stability and is deregulated in leukemia. The activity of Dot1L is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120Ub); however, the detailed mechanism is not understood. We report cryo-EM structures of human Dot1L bound to (1) H2BK120Ub and (2) unmodified nucleosome substrates at 3.5 Å and 4.9 Å, respectively. Comparison of both structures, complemented with biochemical experiments, provides critical insights into the mechanism of Dot1L stimulation by H2BK120Ub. Both structures show Dot1L binding to the same extended surface of the histone octamer. In yeast, this surface is used by silencing proteins involved in heterochromatin formation, explaining the mechanism of their competition with Dot1. These results provide a strong foundation for understanding conserved crosstalk between histone modifications found at actively transcribed genes and offer a general model of how ubiquitin might regulate the activity of chromatin enzymes. | |||||||||
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 | EMマップ: SurfViewMolmilJmol/JSmol |
添付画像 |
-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_0652.map.gz | 115.9 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0652-v30.xml emd-0652.xml | 17.2 KB 17.2 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_0652.png | 155.1 KB | ||
その他 | emd_0652_additional.map.gz emd_0652_half_map_1.map.gz emd_0652_half_map_2.map.gz | 116.1 MB 11.8 MB 11.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0652 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0652 | HTTPS FTP |
-関連構造データ
-リンク
EMDBのページ | EMDB (EBI/PDBe) / EMDataResource |
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「今月の分子」の関連する項目 |
-マップ
ファイル | ダウンロード / ファイル: emd_0652.map.gz / 形式: CCP4 / 大きさ: 125 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Final map from cisTEM, filtered at 3.5A, unsharpened | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.035 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
詳細 | EMDB XML:
CCP4マップ ヘッダ情報:
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-添付データ
-追加マップ: Final map from cisTEM, filtered at 3.3A, -20 bfactor
ファイル | emd_0652_additional.map | ||||||||||||
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注釈 | Final map from cisTEM, filtered at 3.3A, -20 bfactor | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half-map 1
ファイル | emd_0652_half_map_1.map | ||||||||||||
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注釈 | Half-map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Half-map 1
ファイル | emd_0652_half_map_2.map | ||||||||||||
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注釈 | Half-map 1 | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-試料の構成要素
-全体 : Cryo-EM structure of human Dot1L bound to H2BK120Ub nucleosome at...
全体 | 名称: Cryo-EM structure of human Dot1L bound to H2BK120Ub nucleosome at 3.5A resolution |
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要素 |
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-超分子 #1: Cryo-EM structure of human Dot1L bound to H2BK120Ub nucleosome at...
超分子 | 名称: Cryo-EM structure of human Dot1L bound to H2BK120Ub nucleosome at 3.5A resolution タイプ: complex / ID: 1 / 親要素: 0 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
組換発現 | 生物種: Escherichia coli (大腸菌) / 組換株: BL21(DE3) |
-実験情報
-構造解析
手法 | クライオ電子顕微鏡法 |
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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-試料調製
緩衝液 | pH: 7.5 |
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グリッド | 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY / 詳細: unspecified |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 295.15 K / 装置: FEI VITROBOT MARK I 詳細: 3 ul of Dot1L-nucleosome complexes were applied to a glow discharged Quantifoil holey carbon grid (1.2 um hole size, 200 mesh), blotted in a Vitrobot Mark III (FEI Company) using 1.5 seconds ...詳細: 3 ul of Dot1L-nucleosome complexes were applied to a glow discharged Quantifoil holey carbon grid (1.2 um hole size, 200 mesh), blotted in a Vitrobot Mark III (FEI Company) using 1.5 seconds blotting at 100% humidity, and then plunge-frozen in liquid ethane cooled by liquid nitrogen.. |
詳細 | This sample was monodisperse |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: SUPER-RESOLUTION / デジタル化 - サンプリング間隔: 5.0 µm / 平均電子線量: 41.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |
+画像解析
-原子モデル構築 1
精密化 | 空間: REAL / プロトコル: FLEXIBLE FIT |
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得られたモデル | PDB-6o96: |