+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30453 | |||||||||||||||||||||
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タイトル | NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP | |||||||||||||||||||||
マップデータ | ||||||||||||||||||||||
試料 |
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機能・相同性 | 機能・相同性情報 atrial septum secundum morphogenesis / [histone H3]-lysine36 N-dimethyltransferase / histone H4K20 methyltransferase activity / regulation of double-strand break repair via nonhomologous end joining / histone H3K36 dimethyltransferase activity / histone H3K36 trimethyltransferase activity / positive regulation of isotype switching to IgA isotypes / regulation of establishment of protein localization / membranous septum morphogenesis / atrial septum primum morphogenesis ...atrial septum secundum morphogenesis / [histone H3]-lysine36 N-dimethyltransferase / histone H4K20 methyltransferase activity / regulation of double-strand break repair via nonhomologous end joining / histone H3K36 dimethyltransferase activity / histone H3K36 trimethyltransferase activity / positive regulation of isotype switching to IgA isotypes / regulation of establishment of protein localization / membranous septum morphogenesis / atrial septum primum morphogenesis / histone H3K36 methyltransferase activity / histone H3 methyltransferase activity / Nonhomologous End-Joining (NHEJ) / G2/M DNA damage checkpoint / PKMTs methylate histone lysines / bone development / structural constituent of chromatin / nucleosome / double-strand break repair / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / sequence-specific DNA binding / methylation / protein heterodimerization activity / chromatin binding / chromatin / regulation of DNA-templated transcription / nucleolus / negative regulation of transcription by RNA polymerase II / DNA binding / nucleoplasm / nucleus / metal ion binding / cytoplasm 類似検索 - 分子機能 | |||||||||||||||||||||
生物種 | Xenopus laevis (アフリカツメガエル) / Homo sapiens (ヒト) / Xenopus tropicalis (ネッタイツメガエル) | |||||||||||||||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 3.75 Å | |||||||||||||||||||||
データ登録者 | Li W / Tian W / Yuan G / Deng P / Gozani O / Patel D / Wang Z | |||||||||||||||||||||
資金援助 | 中国, 米国, 6件
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引用 | ジャーナル: Nature / 年: 2021 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. | |||||||||||||||||||||
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_30453.map.gz | 35 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30453-v30.xml emd-30453.xml | 23 KB 23 KB | 表示 表示 | EMDBヘッダ |
画像 | emd_30453.png | 134.2 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30453 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30453 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30453_validation.pdf.gz | 470.6 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30453_full_validation.pdf.gz | 470.2 KB | 表示 | |
XML形式データ | emd_30453_validation.xml.gz | 5.9 KB | 表示 | |
CIF形式データ | emd_30453_validation.cif.gz | 6.7 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30453 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30453 | 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_30453.map.gz / 形式: CCP4 / 大きさ: 38.4 MB / タイプ: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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ボクセルのサイズ | X=Y=Z: 1.08 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
-試料の構成要素
+全体 : NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP
+超分子 #1: NSD2 bearing E1099K/T1150A dual mutation in complex with 187-bp NCP
+超分子 #2: Histone H3, H4, H2A and H2B
+超分子 #3: DNA
+超分子 #4: NSD2
+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 NSD2
+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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解析 | 単粒子再構成法 |
試料の集合状態 | particle |
-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. |
-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: FIELD EMISSION GUN |
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 |
-画像解析
最終 再構成 | 解像度のタイプ: BY AUTHOR / 解像度: 3.75 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 使用した粒子像数: 71116 |
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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 |