+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-26809 | |||||||||||||||
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タイトル | KDM2A-nucleosome structure stabilized by H3K36C-UNC8015 covalent conjugate | |||||||||||||||
マップデータ | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate | |||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 histone H3K36me/H3K36me2 demethylase activity / [histone H3]-dimethyl-L-lysine36 demethylase / unmethylated CpG binding / histone H3K36 demethylase activity / negative regulation of transcription by competitive promoter binding / histone demethylase activity / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus ...histone H3K36me/H3K36me2 demethylase activity / [histone H3]-dimethyl-L-lysine36 demethylase / unmethylated CpG binding / histone H3K36 demethylase activity / negative regulation of transcription by competitive promoter binding / histone demethylase activity / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / telomere organization / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / DNAメチル化 / Condensation of Prophase Chromosomes / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / SIRT1 negatively regulates rRNA expression / HCMV Late Events / innate immune response in mucosa / PRC2 methylates histones and DNA / Defective pyroptosis / HDACs deacetylate histones / RNA Polymerase I Promoter Escape / transcription coregulator activity / Nonhomologous End-Joining (NHEJ) / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / circadian regulation of gene expression / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / NoRC negatively regulates rRNA expression / G2/M DNA damage checkpoint / regulation of circadian rhythm / HDMs demethylate histones / B-WICH complex positively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / Metalloprotease DUBs / PKMTs methylate histone lysines / RMTs methylate histone arginines / 遺伝的組換え / Pre-NOTCH Transcription and Translation / nucleosome assembly / double-strand break repair via nonhomologous end joining / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / UCH proteinases / ヌクレオソーム / antimicrobial humoral immune response mediated by antimicrobial peptide / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / RUNX1 regulates transcription of genes involved in differentiation of HSCs / 染色体 / chromatin organization / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / HATs acetylate histones / antibacterial humoral response / Senescence-Associated Secretory Phenotype (SASP) / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / chromosome, telomeric region / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation / regulation of transcription by RNA polymerase II / enzyme binding / protein-containing complex / DNA binding / extracellular space / RNA binding / extracellular exosome / zinc ion binding / extracellular region / 核質 / 生体膜 / identical protein binding / 細胞核 / 細胞質基質 類似検索 - 分子機能 | |||||||||||||||
生物種 | Homo sapiens (ヒト) / 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: 3.2 Å | |||||||||||||||
データ登録者 | Spangler CJ / Skrajna A / Foley CA / Budziszewski GR / Azzam DN / James LI / Frye SV / McGinty RK | |||||||||||||||
資金援助 | 米国, 4件
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引用 | ジャーナル: Nat Chem Biol / 年: 2023 タイトル: Structural basis of paralog-specific KDM2A/B nucleosome recognition. 著者: Cathy J Spangler / Aleksandra Skrajna / Caroline A Foley / Anh Nguyen / Gabrielle R Budziszewski / Dalal N Azzam / Eyla C Arteaga / Holly C Simmons / Charlotte B Smith / Nathaniel A Wesley / ...著者: Cathy J Spangler / Aleksandra Skrajna / Caroline A Foley / Anh Nguyen / Gabrielle R Budziszewski / Dalal N Azzam / Eyla C Arteaga / Holly C Simmons / Charlotte B Smith / Nathaniel A Wesley / Emily M Wilkerson / Jeanne-Marie E McPherson / Dmitri Kireev / Lindsey I James / Stephen V Frye / Dennis Goldfarb / Robert K McGinty / 要旨: The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic ...The nucleosome acidic patch is a major interaction hub for chromatin, providing a platform for enzymes to dock and orient for nucleosome-targeted activities. To define the molecular basis of acidic patch recognition proteome wide, we performed an amino acid resolution acidic patch interactome screen. We discovered that the histone H3 lysine 36 (H3K36) demethylase KDM2A, but not its closely related paralog, KDM2B, requires the acidic patch for nucleosome binding. Despite fundamental roles in transcriptional repression in health and disease, the molecular mechanisms governing nucleosome substrate specificity of KDM2A/B, or any related JumonjiC (JmjC) domain lysine demethylase, remain unclear. We used a covalent conjugate between H3K36 and a demethylase inhibitor to solve cryogenic electron microscopy structures of KDM2A and KDM2B trapped in action on a nucleosome substrate. Our structures show that KDM2-nucleosome binding is paralog specific and facilitated by dynamic nucleosomal DNA unwrapping and histone charge shielding that mobilize the H3K36 sequence for demethylation. | |||||||||||||||
履歴 |
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-構造の表示
添付画像 |
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-ダウンロードとリンク
-EMDBアーカイブ
マップデータ | emd_26809.map.gz | 9.5 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-26809-v30.xml emd-26809.xml | 28.9 KB 28.9 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_26809_fsc.xml | 11.6 KB | 表示 | FSCデータファイル |
画像 | emd_26809.png | 129.1 KB | ||
その他 | emd_26809_additional_1.map.gz emd_26809_half_map_1.map.gz emd_26809_half_map_2.map.gz | 107.3 MB 42.1 MB 42.1 MB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-26809 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-26809 | HTTPS FTP |
-関連構造データ
関連構造データ | 7uv9MC 7uvaC C: 同じ文献を引用 (文献) M: このマップから作成された原子モデル |
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類似構造データ | 類似検索 - 機能・相同性F&H 検索 |
-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_26809.map.gz / 形式: CCP4 / 大きさ: 137.1 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||
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注釈 | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate | ||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 0.91 Å | ||||||||||||||||||||
密度 |
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対称性 | 空間群: 1 | ||||||||||||||||||||
詳細 | EMDB XML:
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-添付データ
-追加マップ: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate multibody...
ファイル | emd_26809_additional_1.map | ||||||||||||
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注釈 | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate multibody refinement nucleosome mask | ||||||||||||
投影像・断面図 |
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密度ヒストグラム |
-ハーフマップ: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half...
ファイル | emd_26809_half_map_1.map | ||||||||||||
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注釈 | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate 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: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half...
ファイル | emd_26809_half_map_2.map | ||||||||||||
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注釈 | KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent conjugate half map 2 | ||||||||||||
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 : KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent co...
+超分子 #1: KDM2A-nucleosome complex stabilized by H3K36C-UNC8015 covalent co...
+分子 #1: Histone H3.2
+分子 #2: Histone H4
+分子 #3: Histone H2A type 1
+分子 #4: Histone H2B type 1-C/E/F/G/I
+分子 #7: Lysine-specific demethylase 2A
+分子 #5: DNA (185-MER)
+分子 #6: DNA (185-MER)
+分子 #8: N-heptanoyl-N-hydroxy-beta-alanine
+分子 #9: FE (III) ION
-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 | 1 mg/mL | |||||||||
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緩衝液 | pH: 7.5 構成要素:
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グリッド | モデル: Quantifoil R1.2/1.3 / 材質: COPPER / 前処理 - タイプ: PLASMA CLEANING / 前処理 - 時間: 60 sec. / 詳細: Tergeo EM plasma cleaner | |||||||||
凍結 | 凍結剤: ETHANE-PROPANE / 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 |
-電子顕微鏡法
顕微鏡 | FEI TALOS ARCTICA |
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電子線 | 加速電圧: 200 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 FIELDBright-field microscopy / 最大 デフォーカス(公称値): 3.0 µm / 最小 デフォーカス(公称値): 0.5 µm / 倍率(公称値): 45000 |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER |
撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 撮影したグリッド数: 1 / 実像数: 9075 / 平均電子線量: 45.0 e/Å2 |
実験機器 | モデル: Talos Arctica / 画像提供: FEI Company |