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基本情報
登録情報 | データベース: PDB / ID: 7kso | ||||||
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タイトル | Cryo-EM structure of PRC2:EZH1-AEBP2-JARID2 | ||||||
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![]() | GENE REGULATION/Transferase / Chromatin / methyltransferase / nucleosome-modifying complex / GENE REGULATION / GENE REGULATION-Transferase complex | ||||||
機能・相同性 | ![]() protein localization to pericentric heterochromatin / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / ubiquitin-modified histone reader activity / facultative heterochromatin formation / histone H3K27 methyltransferase activity / negative regulation of cardiac muscle hypertrophy ...protein localization to pericentric heterochromatin / [histone H3]-lysine27 N-trimethyltransferase / sex chromatin / CAF-1 complex / histone H3K27 trimethyltransferase activity / random inactivation of X chromosome / ubiquitin-modified histone reader activity / facultative heterochromatin formation / histone H3K27 methyltransferase activity / negative regulation of cardiac muscle hypertrophy / negative regulation of cardiac muscle cell proliferation / NURF complex / regulation of cell fate specification / negative regulation of stem cell population maintenance / DNA replication-dependent chromatin assembly / chromatin silencing complex / Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1 / regulation of stem cell differentiation / NuRD complex / ESC/E(Z) complex / Transcription of E2F targets under negative control by DREAM complex / RSC-type complex / Polo-like kinase mediated events / lncRNA binding / cardiac muscle cell proliferation / histone methyltransferase complex / spinal cord development / Sin3-type complex / positive regulation of stem cell population maintenance / histone methyltransferase activity / G1/S-Specific Transcription / ATPase complex / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / RNA Polymerase I Transcription Initiation / negative regulation of cell differentiation / histone deacetylase complex / G0 and Early G1 / subtelomeric heterochromatin formation / anatomical structure morphogenesis / heterochromatin / heterochromatin formation / Cyclin E associated events during G1/S transition / Cyclin A:Cdk2-associated events at S phase entry / nucleosome binding / Deposition of new CENPA-containing nucleosomes at the centromere / spleen development / enzyme activator activity / Regulation of TP53 Activity through Acetylation / methylated histone binding / SUMOylation of chromatin organization proteins / negative regulation of cell migration / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / thymus development / molecular condensate scaffold activity / liver development / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / ubiquitin binding / Defective pyroptosis / cellular response to leukemia inhibitory factor / central nervous system development / HDACs deacetylate histones / stem cell differentiation / hippocampus development / promoter-specific chromatin binding / transcription coregulator activity / negative regulation of transforming growth factor beta receptor signaling pathway / brain development / chromatin DNA binding / PKMTs methylate histone lysines / histone deacetylase binding / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / transcription corepressor activity / nucleosome assembly / chromatin organization / chromosome / histone binding / methylation / regulation of gene expression / Oxidative Stress Induced Senescence / DNA replication / cell population proliferation / Potential therapeutics for SARS / chromosome, telomeric region / nuclear body / chromatin remodeling / ribonucleoprotein complex / cell cycle / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of cell population proliferation / negative regulation of DNA-templated transcription / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription / chromatin / nucleolus / regulation of transcription by RNA polymerase II 類似検索 - 分子機能 | ||||||
生物種 | ![]() | ||||||
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: 3.9 Å | ||||||
![]() | Grau, D.J. / Armache, K.J. | ||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction. 著者: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz ...著者: Daniel Grau / Yixiao Zhang / Chul-Hwan Lee / Marco Valencia-Sánchez / Jenny Zhang / Miao Wang / Marlene Holder / Vladimir Svetlov / Dongyan Tan / Evgeny Nudler / Danny Reinberg / Thomas Walz / Karim-Jean Armache / ![]() ![]() 要旨: Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the ...Polycomb repressive complex 2 (PRC2) is a histone methyltransferase critical for maintaining gene silencing during eukaryotic development. In mammals, PRC2 activity is regulated in part by the selective incorporation of one of two paralogs of the catalytic subunit, EZH1 or EZH2. Each of these enzymes has specialized biological functions that may be partially explained by differences in the multivalent interactions they mediate with chromatin. Here, we present two cryo-EM structures of PRC2:EZH1, one as a monomer and a second one as a dimer bound to a nucleosome. When bound to nucleosome substrate, the PRC2:EZH1 dimer undergoes a dramatic conformational change. We demonstrate that mutation of a divergent EZH1/2 loop abrogates the nucleosome-binding and methyltransferase activities of PRC2:EZH1. Finally, we show that PRC2:EZH1 dimers are more effective than monomers at promoting chromatin compaction, and the divergent EZH1/2 loop is essential for this function, thereby tying together the methyltransferase, nucleosome-binding, and chromatin-compaction activities of PRC2:EZH1. We speculate that the conformational flexibility and the ability to dimerize enable PRC2 to act on the varied chromatin substrates it encounters in the cell. | ||||||
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構造の表示
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構造ビューア | 分子: ![]() ![]() |
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PDBx/mmCIF形式 | ![]() | 352.9 KB | 表示 | ![]() |
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PDB形式 | ![]() | 251.6 KB | 表示 | ![]() |
PDBx/mmJSON形式 | ![]() | ツリー表示 | ![]() | |
その他 | ![]() |
-検証レポート
文書・要旨 | ![]() | 913.6 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 920.9 KB | 表示 | |
XML形式データ | ![]() | 45.9 KB | 表示 | |
CIF形式データ | ![]() | 70.2 KB | 表示 | |
アーカイブディレクトリ | ![]() ![]() | HTTPS FTP |
-関連構造データ
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リンク
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集合体
登録構造単位 | ![]()
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要素
-タンパク質 , 4種, 4分子 ADEF
#1: タンパク質 | 分子量: 85394.141 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q92800, [histone H3]-lysine27 N-trimethyltransferase |
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#4: タンパク質 | 分子量: 47709.527 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q09028 |
#5: タンパク質 | 分子量: 33012.668 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
#6: タンパク質 | 分子量: 138979.719 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() ![]() |
-Polycomb protein ... , 2種, 2分子 BC
#2: タンパク質 | 分子量: 50267.691 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: O75530 |
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#3: タンパク質 | 分子量: 83181.922 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() 発現宿主: ![]() ![]() 参照: UniProt: Q15022 |
-非ポリマー , 1種, 8分子 ![](data/chem/img/ZN.gif)
#7: 化合物 | ChemComp-ZN / |
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-詳細
研究の焦点であるリガンドがあるか | N |
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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 |
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試料調製
構成要素 | 名称: PRC2:EZH1-AEBP2-JARID2 / タイプ: COMPLEX / Entity ID: #1-#6 / 由来: MULTIPLE SOURCES | |||||||||||||||||||||||||
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分子量 | 値: 0.33 MDa / 実験値: NO | |||||||||||||||||||||||||
由来(天然) | 生物種: ![]() | |||||||||||||||||||||||||
緩衝液 | pH: 7.9 | |||||||||||||||||||||||||
緩衝液成分 |
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試料 | 濃度: 0.05 mg/ml / 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 |
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電子顕微鏡撮影
実験機器 | ![]() モデル: Titan Krios / 画像提供: FEI Company |
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顕微鏡 | モデル: FEI TITAN KRIOS |
電子銃 | 電子線源: ![]() |
電子レンズ | モード: BRIGHT FIELD |
撮影 | 電子線照射量: 47 e/Å2 フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) |
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解析
EMソフトウェア |
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CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||
粒子像の選択 | 選択した粒子像数: 1608434 | ||||||||||||
3次元再構成 | 解像度: 3.9 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 211110 / 対称性のタイプ: POINT |