+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-30267 | |||||||||||||||||||||
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タイトル | Human cGAS-nucleosome complex | |||||||||||||||||||||
マップデータ | ||||||||||||||||||||||
試料 |
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キーワード | complex / chromatin / NTase / innate immunity / immunity / nucleosome / cGAS / DNA BINDING PROTEIN / DNA BINDING PROTEIN-DNA complex | |||||||||||||||||||||
機能・相同性 | 機能・相同性情報 cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / regulation of immunoglobulin production / cGAS/STING signaling pathway / pattern recognition receptor signaling pathway / regulation of T cell activation / cytoplasmic pattern recognition receptor signaling pathway ...cyclic GMP-AMP synthase / 2',3'-cyclic GMP-AMP synthase activity / STING mediated induction of host immune responses / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / regulation of immunoglobulin production / cGAS/STING signaling pathway / pattern recognition receptor signaling pathway / regulation of T cell activation / cytoplasmic pattern recognition receptor signaling pathway / negative regulation of cGAS/STING signaling pathway / cGMP-mediated signaling / cellular response to exogenous dsRNA / protein localization to CENP-A containing chromatin / CENP-A containing nucleosome / negative regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of type I interferon production / Replacement of protamines by nucleosomes in the male pronucleus / arachidonate 15-lipoxygenase / arachidonate 15-lipoxygenase activity / nucleosome binding / Packaging Of Telomere Ends / negative regulation of double-strand break repair via homologous recombination / lipoxygenase pathway / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / telomere organization / arachidonate metabolic process / Chromatin modifying enzymes / lipid oxidation / Deposition of new CENPA-containing nucleosomes at the centromere / hepoxilin biosynthetic process / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / linoleic acid metabolic process / Meiotic synapsis / Inhibition of DNA recombination at telomere / positive regulation of defense response to virus by host / nucleosomal DNA binding / RNA Polymerase I Promoter Opening / phosphatidylinositol-4,5-bisphosphate binding / Assembly of the ORC complex at the origin of replication / activation of innate immune response / Interleukin-7 signaling / epigenetic regulation of gene expression / DNA methylation / cAMP-mediated signaling / Condensation of Prophase Chromosomes / HCMV Late Events / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / PRC2 methylates histones and DNA / molecular condensate scaffold activity / Defective pyroptosis / Meiotic recombination / innate immune response in mucosa / DNA Damage/Telomere Stress Induced Senescence / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / determination of adult lifespan / Transcriptional regulation by small RNAs / lipopolysaccharide binding / Transcriptional regulation of granulopoiesis / HDMs demethylate histones / Formation of the beta-catenin:TCF transactivating complex / HCMV Early Events / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / G2/M DNA damage checkpoint / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / PKMTs methylate histone lysines / B-WICH complex positively regulates rRNA expression / heterochromatin formation / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Metalloprotease DUBs / Activation of anterior HOX genes in hindbrain development during early embryogenesis / structural constituent of chromatin / positive regulation of cellular senescence / UCH proteinases / nucleosome / antimicrobial humoral immune response mediated by antimicrobial peptide / Factors involved in megakaryocyte development and platelet production / Processing of DNA double-strand break ends / nucleosome assembly / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / E3 ubiquitin ligases ubiquitinate target proteins / double-stranded DNA binding / Senescence-Associated Secretory Phenotype (SASP) / RUNX1 regulates transcription of genes involved in differentiation of HSCs / HATs acetylate histones / site of double-strand break / gene expression / antibacterial humoral response / Oxidative Stress Induced Senescence / defense response to virus / defense response to Gram-negative bacterium 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: 3.9 Å | |||||||||||||||||||||
データ登録者 | Kujirai T / Zierhut C | |||||||||||||||||||||
資金援助 | 日本, 6件
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引用 | ジャーナル: Science / 年: 2020 タイトル: Structural basis for the inhibition of cGAS by nucleosomes. 著者: Tomoya Kujirai / Christian Zierhut / Yoshimasa Takizawa / Ryan Kim / Lumi Negishi / Nobuki Uruma / Seiya Hirai / Hironori Funabiki / Hitoshi Kurumizaka / 要旨: The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) senses invasion of pathogenic DNA and stimulates inflammatory signaling, autophagy, and apoptosis. Organization of host DNA ...The cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) senses invasion of pathogenic DNA and stimulates inflammatory signaling, autophagy, and apoptosis. Organization of host DNA into nucleosomes was proposed to limit cGAS autoinduction, but the underlying mechanism was unknown. Here, we report the structural basis for this inhibition. In the cryo-electron microscopy structure of the human cGAS-nucleosome core particle (NCP) complex, two cGAS monomers bridge two NCPs by binding the acidic patch of the histone H2A-H2B dimer and nucleosomal DNA. In this configuration, all three known cGAS DNA binding sites, required for cGAS activation, are repurposed or become inaccessible, and cGAS dimerization, another prerequisite for activation, is inhibited. Mutating key residues linking cGAS and the acidic patch alleviates nucleosomal inhibition. This study establishes a structural framework for why cGAS is silenced on chromatinized self-DNA. | |||||||||||||||||||||
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_30267.map.gz | 5.2 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-30267-v30.xml emd-30267.xml | 17.8 KB 17.8 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_30267_fsc.xml | 8.9 KB | 表示 | FSCデータファイル |
画像 | emd_30267.png | 66.9 KB | ||
Filedesc metadata | emd-30267.cif.gz | 6.4 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-30267 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-30267 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_30267_validation.pdf.gz | 411.3 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_30267_full_validation.pdf.gz | 410.8 KB | 表示 | |
XML形式データ | emd_30267_validation.xml.gz | 10.5 KB | 表示 | |
CIF形式データ | emd_30267_validation.cif.gz | 13.8 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30267 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-30267 | 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_30267.map.gz / 形式: CCP4 / 大きさ: 59.6 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: 1.05 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 : Human cGAS-nucleosome complex
全体 | 名称: Human cGAS-nucleosome complex |
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要素 |
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-超分子 #1: Human cGAS-nucleosome complex
超分子 | 名称: Human cGAS-nucleosome complex / タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: #1-#7 |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
-分子 #1: Histone H3.1
分子 | 名称: Histone H3.1 / タイプ: protein_or_peptide / ID: 1 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 15.719445 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: GSHMARTKQT ARKSTGGKAP RKQLATKAAR KSAPATGGVK KPHRYRPGTV ALREIRRYQK STELLIRKLP FQRLVREIAQ DFKTDLRFQ SSAVMALQEA CEAYLVGLFE DTNLCAIHAK RVTIMPKDIQ LARRIRGERA UniProtKB: Histone H3.1 |
-分子 #2: Histone H4
分子 | 名称: Histone H4 / タイプ: protein_or_peptide / ID: 2 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 11.676703 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: GSHMSGRGKG GKGLGKGGAK RHRKVLRDNI QGITKPAIRR LARRGGVKRI SGLIYEETRG VLKVFLENVI RDAVTYTEHA KRKTVTAMD VVYALKRQGR TLYGFGG UniProtKB: Arachidonate 15-lipoxygenase |
-分子 #3: Histone H2A type 1-B/E
分子 | 名称: Histone H2A type 1-B/E / タイプ: protein_or_peptide / ID: 3 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 14.447825 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: GSHMSGRGKQ GGKARAKAKT RSSRAGLQFP VGRVHRLLRK GNYSERVGAG APVYLAAVLE YLTAEILELA GNAARDNKKT RIIPRHLQL AIRNDEELNK LLGRVTIAQG GVLPNIQAVL LPKKTESHHK AKGK UniProtKB: Histone H2A type 1-B/E |
-分子 #4: Histone H2B type 1-J
分子 | 名称: Histone H2B type 1-J / タイプ: protein_or_peptide / ID: 4 / コピー数: 4 / 光学異性体: LEVO |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 14.217516 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: GSHMPEPAKS APAPKKGSKK AVTKAQKKDG KKRKRSRKES YSIYVYKVLK QVHPDTGISS KAMGIMNSFV NDIFERIAGE ASRLAHYNK RSTITSREIQ TAVRLLLPGE LAKHAVSEGT KAVTKYTSAK UniProtKB: Histone H2B type 1-J |
-分子 #7: Cyclic GMP-AMP synthase
分子 | 名称: Cyclic GMP-AMP synthase / タイプ: protein_or_peptide / ID: 7 / コピー数: 2 / 光学異性体: LEVO / EC番号: cyclic GMP-AMP synthase |
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由来(天然) | 生物種: Homo sapiens (ヒト) |
分子量 | 理論値: 44.435191 KDa |
組換発現 | 生物種: Escherichia coli (大腸菌) |
配列 | 文字列: GSPILVRRDA APGASKLRAV LEKLKLSRDD ISTAAGMVKG VVDHLLLRLK CDSAFRGVGL LNTGSYYEHV KISAPNEFDV MFKLEVPRI QLEEYSNTRA YYFVKFKRNP KENPLSQFLE GEILSASKML SKFRKIIKEE INDIKDTDVI MKRKRGGSPA V TLLISEKI ...文字列: GSPILVRRDA APGASKLRAV LEKLKLSRDD ISTAAGMVKG VVDHLLLRLK CDSAFRGVGL LNTGSYYEHV KISAPNEFDV MFKLEVPRI QLEEYSNTRA YYFVKFKRNP KENPLSQFLE GEILSASKML SKFRKIIKEE INDIKDTDVI MKRKRGGSPA V TLLISEKI SVDITLALES KSSWPASTQE GLRIQNWLSA KVRKQLRLKP FYLVPKHAKE GNGFQEETWR LSFSHIEKEI LN NHGKSKT CCENKEEKCC RKDCLKLMKY LLEQLKERFK DKKHLDKFSS YHVKTAFFHV CTQNPQDSQW DRKDLGLCFD NCV TYFLQC LRTEKLENYF IPEFNLFSSN LIDKRSKEFL TKQIEYERNN EFPVFDEFEN LYFQ UniProtKB: Cyclic GMP-AMP synthase |
-分子 #5: DNA (145-MER)
分子 | 名称: DNA (145-MER) / タイプ: dna / ID: 5 / コピー数: 2 / 分類: DNA |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 44.520383 KDa |
配列 | 文字列: (DA)(DT)(DC)(DA)(DG)(DA)(DA)(DT)(DC)(DC) (DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA)(DG) (DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA)(DA) (DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA)(DG) (DA) (DC)(DA)(DG)(DC)(DT) ...文字列: (DA)(DT)(DC)(DA)(DG)(DA)(DA)(DT)(DC)(DC) (DC)(DG)(DG)(DT)(DG)(DC)(DC)(DG)(DA)(DG) (DG)(DC)(DC)(DG)(DC)(DT)(DC)(DA)(DA) (DT)(DT)(DG)(DG)(DT)(DC)(DG)(DT)(DA)(DG) (DA) (DC)(DA)(DG)(DC)(DT)(DC)(DT)(DA) (DG)(DC)(DA)(DC)(DC)(DG)(DC)(DT)(DT)(DA) (DA)(DA) (DC)(DG)(DC)(DA)(DC)(DG)(DT) (DA)(DC)(DG)(DC)(DG)(DC)(DT)(DG)(DT)(DC) (DC)(DC)(DC) (DC)(DG)(DC)(DG)(DT)(DT) (DT)(DT)(DA)(DA)(DC)(DC)(DG)(DC)(DC)(DA) (DA)(DG)(DG)(DG) (DG)(DA)(DT)(DT)(DA) (DC)(DT)(DC)(DC)(DC)(DT)(DA)(DG)(DT)(DC) (DT)(DC)(DC)(DA)(DG) (DG)(DC)(DA)(DC) (DG)(DT)(DG)(DT)(DC)(DA)(DG)(DA)(DT)(DA) (DT)(DA)(DT)(DA)(DC)(DA) (DT)(DC)(DG) (DA)(DT) |
-分子 #6: DNA (145-MER)
分子 | 名称: DNA (145-MER) / タイプ: dna / ID: 6 / コピー数: 2 / 分類: DNA |
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由来(天然) | 生物種: synthetic construct (人工物) |
分子量 | 理論値: 44.99166 KDa |
配列 | 文字列: (DA)(DT)(DC)(DG)(DA)(DT)(DG)(DT)(DA)(DT) (DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC)(DA) (DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG)(DG) (DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG)(DA) (DG) (DT)(DA)(DA)(DT)(DC) ...文字列: (DA)(DT)(DC)(DG)(DA)(DT)(DG)(DT)(DA)(DT) (DA)(DT)(DA)(DT)(DC)(DT)(DG)(DA)(DC)(DA) (DC)(DG)(DT)(DG)(DC)(DC)(DT)(DG)(DG) (DA)(DG)(DA)(DC)(DT)(DA)(DG)(DG)(DG)(DA) (DG) (DT)(DA)(DA)(DT)(DC)(DC)(DC)(DC) (DT)(DT)(DG)(DG)(DC)(DG)(DG)(DT)(DT)(DA) (DA)(DA) (DA)(DC)(DG)(DC)(DG)(DG)(DG) (DG)(DG)(DA)(DC)(DA)(DG)(DC)(DG)(DC)(DG) (DT)(DA)(DC) (DG)(DT)(DG)(DC)(DG)(DT) (DT)(DT)(DA)(DA)(DG)(DC)(DG)(DG)(DT)(DG) (DC)(DT)(DA)(DG) (DA)(DG)(DC)(DT)(DG) (DT)(DC)(DT)(DA)(DC)(DG)(DA)(DC)(DC)(DA) (DA)(DT)(DT)(DG)(DA) (DG)(DC)(DG)(DG) (DC)(DC)(DT)(DC)(DG)(DG)(DC)(DA)(DC)(DC) (DG)(DG)(DG)(DA)(DT)(DT) (DC)(DT)(DG) (DA)(DT) |
-分子 #8: ZINC ION
分子 | 名称: ZINC ION / タイプ: ligand / ID: 8 / コピー数: 2 / 式: ZN |
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分子量 | 理論値: 65.409 Da |
-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
緩衝液 | pH: 7.5 |
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凍結 | 凍結剤: ETHANE |
-電子顕微鏡法
顕微鏡 | TFS KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K3 BIOQUANTUM (6k x 4k) 平均電子線量: 64.0 e/Å2 |
電子線 | 加速電圧: 300 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 FIELD |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |