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基本情報
登録情報 | データベース: EMDB / ID: EMD-30456 | |||||||||||||||||||||
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タイトル | NSD3 bearing E1181K/T1232A dual mutation in complex with 187-bp NCP (2:1 binding mode) | |||||||||||||||||||||
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機能・相同性 | ![]() [histone H3]-lysine4 N-dimethyltransferase / [histone H3]-lysine27 N-dimethyltransferase / histone H3K4 dimethyltransferase activity / histone H3K27 dimethyltransferase activity / histone H3K27 trimethyltransferase activity / histone H3K36 methyltransferase activity / transcription regulator activator activity / histone H3 methyltransferase activity / PKMTs methylate histone lysines / structural constituent of chromatin ...[histone H3]-lysine4 N-dimethyltransferase / [histone H3]-lysine27 N-dimethyltransferase / histone H3K4 dimethyltransferase activity / histone H3K27 dimethyltransferase activity / histone H3K27 trimethyltransferase activity / histone H3K36 methyltransferase activity / transcription regulator activator activity / histone H3 methyltransferase activity / PKMTs methylate histone lysines / structural constituent of chromatin / nucleosome / nucleosome assembly / methylation / protein heterodimerization activity / regulation of DNA-templated transcription / chromatin / positive regulation of DNA-templated transcription / DNA binding / nucleoplasm / nucleus / metal ion binding 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | ![]() ![]() ![]() | |||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.15 Å | |||||||||||||||||||||
![]() | Li W / Tian W / Yuan G / Deng P / Gozani O / Patel D / Wang Z | |||||||||||||||||||||
資金援助 | ![]() ![]()
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![]() | ![]() タイトル: Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases. 著者: Wanqiu Li / Wei Tian / Gang Yuan / Pujuan Deng / Deepanwita Sengupta / Zhongjun Cheng / Yinghua Cao / Jiahao Ren / Yan Qin / Yuqiao Zhou / Yulin Jia / Or Gozani / Dinshaw J Patel / Zhanxin Wang / ![]() ![]() 要旨: Histone methyltransferases of the nuclear receptor-binding SET domain protein (NSD) family, including NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis. ...Histone methyltransferases of the nuclear receptor-binding SET domain protein (NSD) family, including NSD1, NSD2 and NSD3, have crucial roles in chromatin regulation and are implicated in oncogenesis. NSD enzymes exhibit an autoinhibitory state that is relieved by binding to nucleosomes, enabling dimethylation of histone H3 at Lys36 (H3K36). However, the molecular basis that underlies this mechanism is largely unknown. Here we solve the cryo-electron microscopy structures of NSD2 and NSD3 bound to mononucleosomes. We find that binding of NSD2 and NSD3 to mononucleosomes causes DNA near the linker region to unwrap, which facilitates insertion of the catalytic core between the histone octamer and the unwrapped segment of DNA. A network of DNA- and histone-specific contacts between NSD2 or NSD3 and the nucleosome precisely defines the position of the enzyme on the nucleosome, explaining the specificity of methylation to H3K36. Intermolecular contacts between NSD proteins and nucleosomes are altered by several recurrent cancer-associated mutations in NSD2 and NSD3. NSDs that contain these mutations are catalytically hyperactive in vitro and in cells, and their ectopic expression promotes the proliferation of cancer cells and the growth of xenograft tumours. Together, our research provides molecular insights into the nucleosome-based recognition and histone-modification mechanisms of NSD2 and NSD3, which could lead to strategies for therapeutic targeting of proteins of the NSD family. | |||||||||||||||||||||
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構造ビューア | EMマップ: ![]() ![]() ![]() |
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マップデータ | ![]() | 36 MB | ![]() | |
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ヘッダ (付随情報) | ![]() ![]() | 23.7 KB 23.7 KB | 表示 表示 | ![]() |
画像 | ![]() | 91 KB | ||
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文書・要旨 | ![]() | 457.2 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 456.7 KB | 表示 | |
XML形式データ | ![]() | 5.8 KB | 表示 | |
CIF形式データ | ![]() | 6.6 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
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EMDBのページ | ![]() ![]() |
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「今月の分子」の関連する項目 |
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マップ
ファイル | ![]() | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.08 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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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試料の構成要素
+全体 : NSD3 bearing E1181K/T1232A dual mutation in complex with 187-bp N...
+超分子 #1: NSD3 bearing E1181K/T1232A dual mutation in complex with 187-bp N...
+超分子 #2: Histone H3, H4, H2A, H2B
+超分子 #3: DNA
+超分子 #4: NSD3
+分子 #1: Histone H3
+分子 #2: Histone H4
+分子 #3: Histone H2A
+分子 #4: Histone H2B
+分子 #7: Histone-lysine N-methyltransferase NSD3
+分子 #5: DNA (168-MER)
+分子 #6: DNA (168-MER)
+分子 #8: S-ADENOSYLMETHIONINE
+分子 #9: ZINC 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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![]() | 単粒子再構成法 |
試料の集合状態 | particle |
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試料調製
濃度 | 0.3 mg/mL |
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緩衝液 | pH: 7.5 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 281 K / 装置: FEI VITROBOT MARK IV 詳細: blotted for 3 s before being plunged into liquid ethane. |
詳細 | The sample was monodisperse. |
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電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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特殊光学系 | エネルギーフィルター - 名称: GIF Bioquantum / エネルギーフィルター - スリット幅: 20 eV |
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 / 平均電子線量: 50.0 e/Å2 |
電子線 | 加速電圧: 300 kV / 電子線源: ![]() |
電子光学系 | C2レンズ絞り径: 70.0 µm / 照射モード: FLOOD BEAM / 撮影モード: BRIGHT FIELD / Cs: 2.7 mm |
試料ステージ | 試料ホルダーモデル: FEI TITAN KRIOS AUTOGRID HOLDER ホルダー冷却材: NITROGEN |
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.15 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 281815 |
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初期 角度割当 | タイプ: MAXIMUM LIKELIHOOD |
最終 角度割当 | タイプ: MAXIMUM LIKELIHOOD |