+データを開く
-基本情報
登録情報 | データベース: PDB / ID: 6jma | ||||||||||||
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タイトル | cryo-EM structure of DOT1L bound to H2B ubiquitinated nucleosome | ||||||||||||
要素 |
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キーワード | GENE REGULATION (遺伝子発現の調節) / histone (ヒストン) / nucleosome (ヌクレオソーム) / methylation (メチル化) | ||||||||||||
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 / female meiosis I / regulation of receptor signaling pathway via JAK-STAT / histone H3 methyltransferase activity / positive regulation of protein monoubiquitination ...: / 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 / female meiosis I / regulation of receptor signaling pathway via JAK-STAT / histone H3 methyltransferase activity / 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 proteasomal protein catabolic process / heterochromatin formation / energy homeostasis / regulation of neuron apoptotic process / 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 / Endosomal Sorting Complex Required For Transport (ESCRT) / NOTCH2 Activation and Transmission of Signal to the Nucleus / 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 / Regulation of FZD by ubiquitination / 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 / neuron projection morphogenesis / TGF-beta receptor signaling in EMT (epithelial to mesenchymal transition) / N-glycan trimming in the ER and Calnexin/Calreticulin cycle / regulation of mitochondrial membrane potential / 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 / positive regulation of protein ubiquitination / 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 / TNFR2 non-canonical NF-kB pathway / NOTCH3 Activation and Transmission of Signal to the Nucleus / 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 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: 6.8 Å | ||||||||||||
データ登録者 | Jang, S. / Song, J.J. | ||||||||||||
資金援助 | 韓国, 3件
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引用 | ジャーナル: Genes Dev / 年: 2019 タイトル: Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase. 著者: Seongmin Jang / Chanshin Kang / Han-Sol Yang / Taeyang Jung / Hans Hebert / Ka Young Chung / Seung Joong Kim / Sungchul Hohng / Ji-Joon Song / 要旨: DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we ...DOT1L is a histone H3 Lys79 methyltransferase whose activity is stimulated by histone H2B Lys120 ubiquitination, suggesting cross-talk between histone H3 methylation and H2B ubiquitination. Here, we present cryo-EM structures of DOT1L complexes with unmodified or H2B ubiquitinated nucleosomes, showing that DOT1L recognizes H2B ubiquitin and the H2A/H2B acidic patch through a C-terminal hydrophobic helix and an arginine anchor in DOT1L, respectively. Furthermore, the structures combined with single-molecule FRET experiments show that H2B ubiquitination enhances a noncatalytic function of the DOT1L-destabilizing nucleosome. These results establish the molecular basis of the cross-talk between H2B ubiquitination and H3 Lys79 methylation as well as nucleosome destabilization by DOT1L. | ||||||||||||
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 | 6jma.cif.gz | 355.5 KB | 表示 | PDBx/mmCIF形式 |
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PDB形式 | pdb6jma.ent.gz | 271.6 KB | 表示 | PDB形式 |
PDBx/mmJSON形式 | 6jma.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/jm/6jma ftp://data.pdbj.org/pub/pdb/validation_reports/jm/6jma | 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
-タンパク質 , 6種, 10分子 AEBFCGDHXY
#2: タンパク質 | 分子量: 11488.410 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) 発現宿主: Escherichia coli BL21 (大腸菌) / Variant (発現宿主): BL21 / 参照: UniProt: P84233 #3: タンパク質 | 分子量: 9990.770 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) 発現宿主: Escherichia coli BL21 (大腸菌) / Variant (発現宿主): BL21 / 参照: UniProt: P62799 #4: タンパク質 | 分子量: 12660.719 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) 遺伝子: hist1h2aj / 発現宿主: Escherichia coli BL21 (大腸菌) / Variant (発現宿主): BL21 / 参照: UniProt: Q6AZJ8 #5: タンパク質 | 分子量: 10478.032 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) 発現宿主: Escherichia coli BL21 (大腸菌) / Variant (発現宿主): BL21 / 参照: UniProt: P02281 #6: タンパク質 | | 分子量: 37930.039 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 / 発現宿主: Escherichia coli BL21 (大腸菌) / Variant (発現宿主): BL21 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: 8576.831 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: UBB / 発現宿主: Escherichia coli BL21 (大腸菌) / Variant (発現宿主): BL21 / 参照: UniProt: P0CG47 |
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-DNA鎖 / 非ポリマー , 2種, 3分子 IJ
#1: DNA鎖 | 分子量: 35168.547 Da / 分子数: 2 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: Escherichia coli DH5[alpha] (大腸菌) #8: 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 | 名称: DOT1L bound to H2B ubiquitinated nucleosome / タイプ: COMPLEX / Entity ID: #1-#7 / 由来: MULTIPLE SOURCES |
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分子量 | 値: 0.29 MDa / 実験値: NO |
由来(天然) | 生物種: Xenopus laevis (アフリカツメガエル) |
由来(組換発現) | 生物種: Escherichia coli BL21 (大腸菌) |
緩衝液 | pH: 7.5 |
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 |
-電子顕微鏡撮影
顕微鏡 | モデル: FEI TITAN |
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電子銃 | 電子線源: FIELD EMISSION GUN / 加速電圧: 300 kV / 照射モード: OTHER |
電子レンズ | モード: BRIGHT FIELDBright-field microscopy |
撮影 | 電子線照射量: 37.28 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
-解析
CTF補正 | タイプ: PHASE FLIPPING ONLY |
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3次元再構成 | 解像度: 6.8 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 122242 / 対称性のタイプ: POINT |
原子モデル構築 | プロトコル: FLEXIBLE FIT |