+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6nqa | ||||||
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タイトル | Active state Dot1L bound to the H2B-Ubiquitinated nucleosome, 1-to-1 complex | ||||||
要素 |
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キーワード | STRUCTURAL PROTEIN/TRANSFERASE/DNA (構造) / Ubiquitin (ユビキチン) / Nucleosome (ヌクレオソーム) / Methyltransferase (メチルトランスフェラーゼ) / STRUCTURAL PROTEIN-TRANSFERASE-DNA complex (構造) | ||||||
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 / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / histone methyltransferase activity / heterochromatin formation / Maturation of protein E ...: / histone H3K79 trimethyltransferase activity / [histone H3]-lysine79 N-trimethyltransferase / histone H3K79 methyltransferase activity / regulation of transcription regulatory region DNA binding / histone H3 methyltransferase activity / regulation of receptor signaling pathway via JAK-STAT / histone methyltransferase activity / heterochromatin formation / 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 / グリコーゲン合成 / IRAK1 recruits IKK complex / IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation / Membrane binding and targetting of GAG proteins / Constitutive Signaling by NOTCH1 HD Domain Mutants / NOTCH2 Activation and Transmission of Signal to the Nucleus / Endosomal Sorting Complex Required For Transport (ESCRT) / IRAK2 mediated activation of TAK1 complex upon TLR7/8 or 9 stimulation / Regulation of FZD by ubiquitination / PTK6 Regulates RTKs and Their Effectors AKT1 and DOK1 / Negative regulation of FLT3 / TICAM1,TRAF6-dependent induction of TAK1 complex / TICAM1-dependent activation of IRF3/IRF7 / APC/C:Cdc20 mediated degradation of Cyclin B / Downregulation of ERBB4 signaling / p75NTR recruits signalling complexes / TRAF6 mediated IRF7 activation in TLR7/8 or 9 signaling / APC-Cdc20 mediated degradation of Nek2A / PINK1-PRKN Mediated Mitophagy / TRAF6-mediated induction of TAK1 complex within TLR4 complex / InlA-mediated entry of Listeria monocytogenes into host cells / Pexophagy / telomere organization / Regulation of innate immune responses to cytosolic DNA / VLDLR internalisation and degradation / Downregulation of ERBB2:ERBB3 signaling / NRIF signals cell death from the nucleus / Activated NOTCH1 Transmits Signal to the Nucleus / Translesion synthesis by REV1 / NF-kB is activated and signals survival / Regulation of PTEN localization / Translesion synthesis by POLK / Regulation of BACH1 activity / Synthesis of active ubiquitin: roles of E1 and E2 enzymes / Translesion synthesis by POLI / Gap-filling DNA repair synthesis and ligation in GG-NER / MAP3K8 (TPL2)-dependent MAPK1/3 activation / TICAM1, RIP1-mediated IKK complex recruitment / Downregulation of TGF-beta receptor signaling / Josephin domain DUBs / Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE) / 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 / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / Autodegradation of Cdh1 by Cdh1:APC/C / TNFR1-induced NF-kappa-B signaling pathway / DNA damage checkpoint signaling / 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 / Regulation of NF-kappa B signaling / NIK-->noncanonical NF-kB signaling / Ubiquitin-dependent degradation of Cyclin D / AUF1 (hnRNP D0) binds and destabilizes mRNA / Negative regulators of DDX58/IFIH1 signaling / NOTCH3 Activation and Transmission of Signal to the Nucleus / TNFR2 non-canonical NF-kB pathway / activated TAK1 mediates p38 MAPK activation / Assembly of the pre-replicative complex / Vpu mediated degradation of CD4 / Deactivation of the beta-catenin transactivating complex / Degradation of DVL / Ubiquitin Mediated Degradation of Phosphorylated Cdc25A / Recognition of DNA damage by PCNA-containing replication complex / Regulation of signaling by CBL / Dectin-1 mediated noncanonical NF-kB signaling / Hh mutants are degraded by ERAD / Cdc20:Phospho-APC/C mediated degradation of Cyclin A / Fanconi Anemia Pathway / Negative regulation of FGFR3 signaling / Peroxisomal protein import / Termination of translesion DNA synthesis / Degradation of AXIN / Downregulation of SMAD2/3:SMAD4 transcriptional activity / Regulation of TNFR1 signaling / Defective CFTR causes cystic fibrosis / Degradation of GLI1 by the proteasome / Activation of NF-kappaB in B cells / Hedgehog ligand biogenesis 類似検索 - 分子機能 | ||||||
生物種 | synthetic construct (人工物) Xenopus laevis (アフリカツメガエル) 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: 3.54 Å | ||||||
データ登録者 | Worden, E.J. / Hoffmann, N.A. / 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 | 分子: MolmilJmol/JSmol |
-ダウンロードとリンク
-ダウンロード
PDBx/mmCIF形式 | 6nqa.cif.gz | 400 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6nqa.ent.gz | 313.3 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6nqa.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
アーカイブディレクトリ | https://data.pdbj.org/pub/pdb/validation_reports/nq/6nqa ftp://data.pdbj.org/pub/pdb/validation_reports/nq/6nqa | HTTPS FTP |
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-関連構造データ
-リンク
-集合体
登録構造単位 |
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-要素
-601 DNA Strand ... , 2種, 2分子 IJ
#1: DNA鎖 | 分子量: 44825.559 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / プラスミド: pST55-16x601 / 発現宿主: Escherichia coli (大腸菌) |
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#2: DNA鎖 | 分子量: 45305.852 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / プラスミド: pST55-16x601 / 発現宿主: Escherichia coli (大腸菌) |
-タンパク質 , 6種, 10分子 FBGCHDKLEA
#3: タンパク質 | 分子量: 11263.231 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) Xenopus laevis (アフリカツメガエル) プラスミド: pET3a / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P62799 #4: タンパク質 | 分子量: 13978.241 Da / 分子数: 2 / Mutation: G99R, A123S / 由来タイプ: 組換発現 由来: (組換発現) Xenopus laevis (アフリカツメガエル) プラスミド: pET3a / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P06897 #5: タンパク質 | 分子量: 13498.715 Da / 分子数: 2 / Mutation: S32T, K120C / 由来タイプ: 組換発現 由来: (組換発現) Xenopus laevis (アフリカツメガエル) プラスミド: pET3a / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P02281 #6: タンパク質 | | 分子量: 47432.012 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: DOT1L, KIAA1814, KMT4 / プラスミド: pET32a / 発現宿主: Escherichia coli (大腸菌) 参照: UniProt: Q8TEK3, ヒストンメチルトランスフェラーゼ #7: タンパク質 | | 分子量: 9036.393 Da / 分子数: 1 / Mutation: G76C / 由来タイプ: 組換発現 / 由来: (組換発現) Homo sapiens (ヒト) / 遺伝子: UBC / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P0CG48 #8: タンパク質 | 分子量: 15251.830 Da / 分子数: 2 / Mutation: G102A, K79Nle, M90Nle, M120Nle / 由来タイプ: 組換発現 由来: (組換発現) Xenopus laevis (アフリカツメガエル) プラスミド: pQE-81L / 発現宿主: Escherichia coli (大腸菌) / 参照: UniProt: P84233 |
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-非ポリマー , 1種, 1分子
#9: 化合物 | ChemComp-SAM / |
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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 |
-試料調製
構成要素 |
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分子量 | 実験値: NO | |||||||||||||||||||||||||||||||||||||||||||||||||
由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.5 詳細: Solutions were prepared on the day of freezing and filtered though a 0.2 um filter prior to use. | |||||||||||||||||||||||||||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.75 mg/ml / 包埋: NO / シャドウイング: NO / 染色: NO / 凍結: YES / 詳細: Crosslinked with glutaraldehyde | |||||||||||||||||||||||||||||||||||||||||||||||||
試料支持 | グリッドの材料: COPPER / グリッドのサイズ: 400 divisions/in. / グリッドのタイプ: C-flat-2/2 | |||||||||||||||||||||||||||||||||||||||||||||||||
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: Blot once for 3.5 seconds before freezing. |
-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: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: FLOOD BEAM |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy / 倍率(公称値): 130000 X / 最大 デフォーカス(公称値): 2500 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: 100 µm |
試料ホルダ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | 平均露光時間: 8.2 sec. / 電子線照射量: 50 e/Å2 / 検出モード: SUPER-RESOLUTION フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 撮影したグリッド数: 2 / 実像数: 2284 / 詳細: 3 exposures per hole |
画像スキャン | 動画フレーム数/画像: 40 / 利用したフレーム数/画像: 1-40 |
-解析
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: 654532 | ||||||||||||||||||||||||||||||||||||||||||||||||||||
対称性 | 点対称性: C1 (非対称) | ||||||||||||||||||||||||||||||||||||||||||||||||||||
3次元再構成 | 解像度: 3.54 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 220681 / 対称性のタイプ: POINT | ||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 | プロトコル: OTHER / 空間: REAL | ||||||||||||||||||||||||||||||||||||||||||||||||||||
原子モデル構築 |
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