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基本情報
登録情報 | データベース: PDB / ID: 7at8 | |||||||||
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タイトル | Histone H3 recognition by nucleosome-bound PRC2 subunit EZH2. | |||||||||
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![]() | GENE REGULATION / Polycomb / nucleosome / histone methyltransferase / PRC2 / EZH2 / H3K36 / H3 tail / H3 / histone H3 / Polycomb Repressive Complex 2 / cryo-EM / nucleosome recognition / H3K36me2 / H3K36me3 | |||||||||
機能・相同性 | ![]() negative regulation of epidermal cell differentiation / : / : / transcription corepressor binding => GO:0001222 / subtelomeric heterochromatin formation => GO:0031509 / : / : / : / regulation of kidney development / hepatocyte homeostasis ...negative regulation of epidermal cell differentiation / : / : / transcription corepressor binding => GO:0001222 / subtelomeric heterochromatin formation => GO:0031509 / : / : / : / regulation of kidney development / hepatocyte homeostasis / cellular response to trichostatin A / regulation of gliogenesis / [histone H3]-lysine27 N-trimethyltransferase / negative regulation of striated muscle cell differentiation / sex chromatin / negative regulation of keratinocyte differentiation / histone H3K27 trimethyltransferase activity / negative regulation of retinoic acid receptor signaling pathway / random inactivation of X chromosome / primary miRNA binding / skeletal muscle satellite cell maintenance involved in skeletal muscle regeneration / response to tetrachloromethane / cerebellar cortex development / facultative heterochromatin formation / histone H3K27 methyltransferase activity / positive regulation of cell cycle G1/S phase transition / chromatin => GO:0000785 / negative regulation of G0 to G1 transition / chromatin silencing complex / ESC/E(Z) complex / protein-lysine N-methyltransferase activity / negative regulation of stem cell differentiation / RSC-type complex / pronucleus / cardiac muscle hypertrophy in response to stress / synaptic transmission, GABAergic / lncRNA binding / positive regulation of dendrite development / histone H3 methyltransferase activity / negative regulation of gene expression, epigenetic / G1 to G0 transition / negative regulation of G1/S transition of mitotic cell cycle / histone methyltransferase activity / oligodendrocyte differentiation / Transcriptional Regulation by E2F6 / negative regulation of transcription elongation by RNA polymerase II / negative regulation of cell differentiation / subtelomeric heterochromatin formation / negative regulation of cytokine production involved in inflammatory response / RNA polymerase II core promoter sequence-specific DNA binding / pericentric heterochromatin / ribonucleoprotein complex binding / heterochromatin formation / positive regulation of epithelial to mesenchymal transition / keratinocyte differentiation / enzyme activator activity / protein localization to chromatin / methylated histone binding / SUMOylation of chromatin organization proteins / B cell differentiation / transcription corepressor binding / positive regulation of GTPase activity / PRC2 methylates histones and DNA / Regulation of PTEN gene transcription / Defective pyroptosis / liver regeneration / stem cell differentiation / hippocampus development / promoter-specific chromatin binding / positive regulation of MAP kinase activity / protein modification process / positive regulation of protein serine/threonine kinase activity / regulation of circadian rhythm / negative regulation of DNA-binding transcription factor activity / chromatin DNA binding / PKMTs methylate histone lysines / cellular response to hydrogen peroxide / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / G1/S transition of mitotic cell cycle / structural constituent of chromatin / transcription corepressor activity / nucleosome / rhythmic process / nucleosome assembly / response to estradiol / chromatin organization / methylation / Oxidative Stress Induced Senescence / cell population proliferation / chromosome, telomeric region / nuclear body / ribonucleoprotein complex / protein heterodimerization activity / RNA polymerase II cis-regulatory region sequence-specific DNA binding / negative regulation of DNA-templated transcription / synapse / chromatin binding / positive regulation of cell population proliferation / regulation of DNA-templated transcription 類似検索 - 分子機能 | |||||||||
生物種 | ![]() ![]() synthetic construct (人工物) | |||||||||
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: 4.4 Å | |||||||||
![]() | Finogenova, K. / Benda, C. / Schaefer, I.B. / Poepsel, S. / Strauss, M. / Mueller, J. | |||||||||
資金援助 | ![]()
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![]() | ![]() タイトル: Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3. 著者: Ksenia Finogenova / Jacques Bonnet / Simon Poepsel / Ingmar B Schäfer / Katja Finkl / Katharina Schmid / Claudia Litz / Mike Strauss / Christian Benda / Jürg Müller / ![]() ![]() 要旨: Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 ...Repression of genes by Polycomb requires that PRC2 modifies their chromatin by trimethylating lysine 27 on histone H3 (H3K27me3). At transcriptionally active genes, di- and tri-methylated H3K36 inhibit PRC2. Here, the cryo-EM structure of PRC2 on dinucleosomes reveals how binding of its catalytic subunit EZH2 to nucleosomal DNA orients the H3 N-terminus via an extended network of interactions to place H3K27 into the active site. Unmodified H3K36 occupies a critical position in the EZH2-DNA interface. Mutation of H3K36 to arginine or alanine inhibits H3K27 methylation by PRC2 on nucleosomes . Accordingly, H3K36A and H3K36R mutants show reduced levels of H3K27me3 and defective Polycomb repression of HOX genes. The relay of interactions between EZH2, the nucleosomal DNA and the H3 N-terminus therefore creates the geometry that permits allosteric inhibition of PRC2 by methylated H3K36 in transcriptionally active chromatin. | |||||||||
履歴 |
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構造の表示
ムービー |
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構造ビューア | 分子: ![]() ![]() |
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ダウンロードとリンク
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PDBx/mmCIF形式 | ![]() | 400.6 KB | 表示 | ![]() |
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PDB形式 | ![]() | 295.1 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 | ![]() | 835.4 KB | 表示 | ![]() |
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文書・詳細版 | ![]() | 855.9 KB | 表示 | |
XML形式データ | ![]() | 42.2 KB | 表示 | |
CIF形式データ | ![]() | 66.7 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 , 6種, 10分子 ACDHEIFJGK
#1: タンパク質 | 分子量: 87195.328 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) ![]() ![]() 参照: UniProt: Q15910-2, UniProt: Q15910*PLUS, [histone H3]-lysine27 N-trimethyltransferase | ||||||
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#2: 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) ![]() ![]() | ||||||
#3: タンパク質 | 分子量: 15303.930 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 発現宿主: ![]() ![]() #4: タンパク質 | 分子量: 11263.231 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 発現宿主: ![]() ![]() #5: タンパク質 | 分子量: 13978.241 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 遺伝子: hist1h2aj, LOC494591 / 発現宿主: ![]() ![]() #6: タンパク質 | 分子量: 13524.752 Da / 分子数: 2 / 由来タイプ: 組換発現 由来: (組換発現) ![]() 発現宿主: ![]() ![]() |
-Widom601 DNA plus ... , 2種, 2分子 TU
#7: DNA鎖 | 分子量: 47904.535 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: ![]() ![]() |
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#8: DNA鎖 | 分子量: 48402.852 Da / 分子数: 1 / 由来タイプ: 組換発現 / 由来: (組換発現) synthetic construct (人工物) / 発現宿主: ![]() ![]() |
-非ポリマー , 2種, 8分子 ![](data/chem/img/ZN.gif)
![](data/chem/img/SAH.gif)
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#9: 化合物 | ChemComp-ZN / #10: 化合物 | ChemComp-SAH / | |
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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 |
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由来(天然) |
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由来(組換発現) |
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緩衝液 | pH: 7.8 | ||||||||||||||||||||||||||||||
試料 | 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-PROPANE |
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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: 52.96 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
CTF補正 | タイプ: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3次元再構成 | 解像度: 4.4 Å / 解像度の算出法: FSC 0.143 CUT-OFF / 粒子像の数: 45849 / 対称性のタイプ: POINT |