+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-0694 | |||||||||
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タイトル | Cryo-EM structure of human MLL1-NCP complex, binding mode1 | |||||||||
マップデータ | Main map of human MLL1-NCP complex, binding mode1 | |||||||||
試料 |
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キーワード | histone modification / nucleosome / MLL / TRANSCRIPTION / TRANSCRIPTION-DNA complex | |||||||||
機能・相同性 | 機能・相同性情報 protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / T-helper 2 cell differentiation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity ...protein-cysteine methyltransferase activity / response to potassium ion / [histone H3]-lysine4 N-methyltransferase / histone H3K4 monomethyltransferase activity / unmethylated CpG binding / histone H3K4 trimethyltransferase activity / negative regulation of DNA methylation-dependent heterochromatin formation / T-helper 2 cell differentiation / MLL3/4 complex / regulation of short-term neuronal synaptic plasticity / Set1C/COMPASS complex / MLL1/2 complex / definitive hemopoiesis / ATAC complex / NSL complex / histone H3K4 methyltransferase activity / Cardiogenesis / embryonic hemopoiesis / exploration behavior / anterior/posterior pattern specification / regulation of tubulin deacetylation / histone methyltransferase complex / Formation of WDR5-containing histone-modifying complexes / regulation of cell division / minor groove of adenine-thymine-rich DNA binding / membrane depolarization / regulation of embryonic development / hemopoiesis / MLL1 complex / histone acetyltransferase complex / negative regulation of fibroblast proliferation / homeostasis of number of cells within a tissue / positive regulation of gluconeogenesis / spleen development / lysine-acetylated histone binding / cellular response to transforming growth factor beta stimulus / methylated histone binding / transcription initiation-coupled chromatin remodeling / 転移酵素; 一炭素原子の基を移すもの; メチル基を移すもの / post-embryonic development / skeletal system development / gluconeogenesis / Deactivation of the beta-catenin transactivating complex / Transcriptional regulation of granulopoiesis / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / circadian regulation of gene expression / PKMTs methylate histone lysines / visual learning / protein modification process / euchromatin / RMTs methylate histone arginines / mitotic spindle / Activation of anterior HOX genes in hindbrain development during early embryogenesis / beta-catenin binding / response to estrogen / structural constituent of chromatin / nucleosome / nucleosome assembly / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Neddylation / HATs acetylate histones / histone binding / fibroblast proliferation / protein-containing complex assembly / methylation / transcription cis-regulatory region binding / regulation of cell cycle / protein heterodimerization activity / chromatin binding / positive regulation of cell population proliferation / DNA damage response / regulation of transcription by RNA polymerase II / positive regulation of DNA-templated transcription / regulation of DNA-templated transcription / nucleolus / apoptotic process / negative regulation of transcription by RNA polymerase II / positive regulation of transcription by RNA polymerase II / protein homodimerization activity / DNA binding / zinc ion binding / nucleoplasm / identical protein binding / nucleus / metal ion binding / cytosol 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: 4.1 Å | |||||||||
データ登録者 | Huang J / Xue H | |||||||||
資金援助 | 中国, 1件
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引用 | ジャーナル: Nature / 年: 2019 タイトル: Structural basis of nucleosome recognition and modification by MLL methyltransferases. 著者: Han Xue / Tonghui Yao / Mi Cao / Guanjun Zhu / Yan Li / Guiyong Yuan / Yong Chen / Ming Lei / Jing Huang / 要旨: Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and ...Methyltransferases of the mixed-lineage leukaemia (MLL) family-which include MLL1, MLL2, MLL3, MLL4, SET1A and SET1B-implement methylation of histone H3 on lysine 4 (H3K4), and have critical and distinct roles in the regulation of transcription in haematopoiesis, adipogenesis and development. The C-terminal catalytic SET (Su(var.)3-9, enhancer of zeste and trithorax) domains of MLL proteins are associated with a common set of regulatory factors (WDR5, RBBP5, ASH2L and DPY30) to achieve specific activities. Current knowledge of the regulation of MLL activity is limited to the catalysis of histone H3 peptides, and how H3K4 methyl marks are deposited on nucleosomes is poorly understood. H3K4 methylation is stimulated by mono-ubiquitination of histone H2B on lysine 120 (H2BK120ub1), a prevalent histone H2B mark that disrupts chromatin compaction and favours open chromatin structures, but the underlying mechanism remains unknown. Here we report cryo-electron microscopy structures of human MLL1 and MLL3 catalytic modules associated with nucleosome core particles that contain H2BK120ub1 or unmodified H2BK120. These structures demonstrate that the MLL1 and MLL3 complexes both make extensive contacts with the histone-fold and DNA regions of the nucleosome; this allows ease of access to the histone H3 tail, which is essential for the efficient methylation of H3K4. The H2B-conjugated ubiquitin binds directly to RBBP5, orienting the association between MLL1 or MLL3 and the nucleosome. The MLL1 and MLL3 complexes display different structural organizations at the interface between the WDR5, RBBP5 and MLL1 (or the corresponding MLL3) subunits, which accounts for the opposite roles of WDR5 in regulating the activity of the two enzymes. These findings transform our understanding of the structural basis for the regulation of MLL activity at the nucleosome level, and highlight the pivotal role of nucleosome regulation in histone-tail modification. | |||||||||
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_0694.map.gz | 70.3 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-0694-v30.xml emd-0694.xml | 24.4 KB 24.4 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_0694_fsc.xml | 9.7 KB | 表示 | FSCデータファイル |
画像 | emd_0694.png | 211.6 KB | ||
マスクデータ | emd_0694_msk_1.map | 75.1 MB | マスクマップ | |
Filedesc metadata | emd-0694.cif.gz | 7.5 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-0694 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-0694 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_0694_validation.pdf.gz | 622.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_0694_full_validation.pdf.gz | 621.9 KB | 表示 | |
XML形式データ | emd_0694_validation.xml.gz | 10.9 KB | 表示 | |
CIF形式データ | emd_0694_validation.cif.gz | 14.5 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0694 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-0694 | 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_0694.map.gz / 形式: CCP4 / 大きさ: 75.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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注釈 | Main map of human MLL1-NCP complex, binding mode1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.1 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_0694_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 |
-試料の構成要素
+全体 : Human MLL1 complex associated with an unmodified nucleosome, bind...
+超分子 #1: Human MLL1 complex associated with an unmodified nucleosome, bind...
+超分子 #2: Human MLL1 complex
+超分子 #3: unmodified nucleosome
+分子 #1: Histone H3
+分子 #2: Histone H4
+分子 #3: Histone H2A
+分子 #4: Histone H2B 1.1
+分子 #7: Retinoblastoma-binding protein 5
+分子 #8: Histone-lysine N-methyltransferase 2A
+分子 #9: WD repeat-containing protein 5
+分子 #10: Set1/Ash2 histone methyltransferase complex subunit ASH2
+分子 #5: DNA (145-MER)
+分子 #6: DNA (145-MER)
+分子 #11: S-ADENOSYL-L-HOMOCYSTEINE
+分子 #12: ZINC ION
+分子 #13: LYSINE
+分子 #14: GLUTAMINE
-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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凍結 | 凍結剤: ETHANE |
-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 K3 (6k x 4k) / 平均電子線量: 45.0 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 |