+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-9384 | |||||||||
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タイトル | Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 2-to-1 complex | |||||||||
マップデータ | Sharpened map for the structure of Dot1L bound to a ubiquitinated nucleosome | |||||||||
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 / telomere organization / neuron projection morphogenesis / 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 / NOTCH3 Activation and Transmission of Signal to the Nucleus / 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 / EGFR downregulation / 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 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Xenopus laevis (アフリカツメガエル) / synthetic construct (人工物) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 2.96 Å | |||||||||
データ登録者 | Worden EJ / Hoffmann NA / Wolberger C | |||||||||
資金援助 | 米国, 1件
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引用 | ジャーナル: Cell / 年: 2019 タイトル: Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L. 著者: Evan J Worden / Niklas A Hoffmann / Chad W Hicks / Cynthia Wolberger / 要旨: Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is ...Methylation of histone H3 K79 by Dot1L is a hallmark of actively transcribed genes that depends on monoubiquitination of H2B K120 (H2B-Ub) and is an example of histone modification cross-talk that is conserved from yeast to humans. We report here cryo-EM structures of Dot1L bound to ubiquitinated nucleosome that show how H2B-Ub stimulates Dot1L activity and reveal a role for the histone H4 tail in positioning Dot1L. We find that contacts mediated by Dot1L and the H4 tail induce a conformational change in the globular core of histone H3 that reorients K79 from an inaccessible position, thus enabling this side chain to insert into the active site in a position primed for catalysis. Our study provides a comprehensive mechanism of cross-talk between histone ubiquitination and methylation and reveals structural plasticity in histones that makes it possible for histone-modifying enzymes to access residues within the nucleosome core. | |||||||||
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_9384.map.gz | 5.6 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-9384-v30.xml emd-9384.xml | 36 KB 36 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_9384_fsc.xml | 9.1 KB | 表示 | FSCデータファイル |
画像 | emd_9384.png | 184.4 KB | ||
マスクデータ | emd_9384_msk_1.map | 64 MB | マスクマップ | |
その他 | emd_9384_additional.map.gz emd_9384_additional_1.map.gz emd_9384_half_map_1.map.gz emd_9384_half_map_2.map.gz | 48.2 MB 48.2 MB 59.8 MB 59.8 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-9384 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-9384 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_9384_validation.pdf.gz | 620.9 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_9384_full_validation.pdf.gz | 620.5 KB | 表示 | |
XML形式データ | emd_9384_validation.xml.gz | 16.2 KB | 表示 | |
CIF形式データ | emd_9384_validation.cif.gz | 21.1 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9384 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-9384 | 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_9384.map.gz / 形式: CCP4 / 大きさ: 64 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Sharpened map for the structure of Dot1L bound to a ubiquitinated nucleosome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.064 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
-マスク #1
ファイル | emd_9384_msk_1.map | ||||||||||||
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投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Unsharpened map for the structure of Dot1L bound...
ファイル | emd_9384_additional.map | ||||||||||||
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注釈 | Unsharpened map for the structure of Dot1L bound to a ubiquitinated nucleosome | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-追加マップ: Unsharpened map for the structure of Dot1L bound...
ファイル | emd_9384_additional_1.map | ||||||||||||
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注釈 | Unsharpened map for the structure of Dot1L bound to a ubiquitinated nucleosome | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Sharpened half map used for structure building and refinement
ファイル | emd_9384_half_map_1.map | ||||||||||||
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注釈 | Sharpened half map used for structure building and refinement | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: Sharpened half map used for structure validation
ファイル | emd_9384_half_map_2.map | ||||||||||||
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注釈 | Sharpened half map used for structure validation | ||||||||||||
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 : Active state Dot1L in complex with the H2B-Ub nucleosome
+超分子 #1: Active state Dot1L in complex with the H2B-Ub nucleosome
+超分子 #2: Dot1L
+超分子 #3: H2H2B-Ub nucleosome
+超分子 #4: histone core
+超分子 #5: ubiquitin
+超分子 #6: DNA
+分子 #1: Histone H3.2
+分子 #2: Histone H4
+分子 #3: Histone H2A type 1
+分子 #4: Histone H2B 1.1
+分子 #7: Histone-lysine N-methyltransferase, H3 lysine-79 specific
+分子 #8: Ubiquitin
+分子 #5: 601 DNA Strand 1
+分子 #6: 601 DNA Strand 2
+分子 #9: S-ADENOSYLMETHIONINE
-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
濃度 | 0.75 mg/mL | ||||||||||||
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緩衝液 | pH: 7.5 構成要素:
詳細: Solutions were prepared on the day of freezing and filtered though a 0.2 um filter prior to use. | ||||||||||||
グリッド | モデル: C-flat-2/2 / 材質: COPPER / メッシュ: 400 / 支持フィルム - 材質: CARBON / 支持フィルム - トポロジー: HOLEY ARRAY / 前処理 - タイプ: GLOW DISCHARGE / 前処理 - 雰囲気: AIR | ||||||||||||
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 277 K / 装置: FEI VITROBOT MARK IV / 詳細: Blot once for 3.5 seconds before freezing.. | ||||||||||||
詳細 | Crosslinked with glutaraldehyde |
-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 - 画像ごとのフレーム数: 1-40 / 撮影したグリッド数: 2 / 実像数: 2284 / 平均露光時間: 8.2 sec. / 平均電子線量: 50.0 e/Å2 / 詳細: 3 exposures per hole |
電子線 | 加速電圧: 300 kV / 電子線源: FIELD EMISSION GUN |
電子光学系 | C2レンズ絞り径: 100.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm / 最大 デフォーカス(公称値): 2.5 µm / 最小 デフォーカス(公称値): 1.0 µm / 倍率(公称値): 130000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
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
初期モデル |
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精密化 | 空間: REAL / プロトコル: OTHER | ||||||||||||||||||||||||||
得られたモデル | PDB-6nj9: |