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万見- EMDB-22206: Two mouse cGAS catalytic domain binding to human assembled nucleosome -
+データを開く
-基本情報
登録情報 | データベース: EMDB / ID: EMD-22206 | |||||||||
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タイトル | Two mouse cGAS catalytic domain binding to human assembled nucleosome | |||||||||
マップデータ | two mouse cGAS binds to reconstituted human nucleosome | |||||||||
試料 |
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キーワード | Immunity / IMMUNE SYSTEM / IMMUNE SYSTEM-DNA complex | |||||||||
機能・相同性 | 機能・相同性情報 2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / regulation of type I interferon production / regulation of immunoglobulin production / cGAS/STING signaling pathway / regulation of T cell activation / negative regulation of cGAS/STING signaling pathway / negative regulation of DNA repair ...2',3'-cyclic GMP-AMP synthase activity / cyclic GMP-AMP synthase / paracrine signaling / poly-ADP-D-ribose modification-dependent protein binding / regulation of type I interferon production / regulation of immunoglobulin production / cGAS/STING signaling pathway / regulation of T cell activation / negative regulation of cGAS/STING signaling pathway / negative regulation of DNA repair / cGMP-mediated signaling / cellular response to exogenous dsRNA / positive regulation of type I interferon production / nucleosome binding / regulation of immune response / negative regulation of double-strand break repair via homologous recombination / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / positive regulation of defense response to virus by host / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / Packaging Of Telomere Ends / activation of innate immune response / phosphatidylinositol-4,5-bisphosphate binding / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / Deposition of new CENPA-containing nucleosomes at the centromere / nucleosomal DNA binding / cAMP-mediated signaling / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / telomere organization / Meiotic synapsis / Interleukin-7 signaling / RNA Polymerase I Promoter Opening / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / Regulation of endogenous retroelements by the Human Silencing Hub (HUSH) complex / DNA methylation / Condensation of Prophase Chromosomes / SIRT1 negatively regulates rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / HCMV Late Events / innate immune response in mucosa / determination of adult lifespan / PRC2 methylates histones and DNA / Regulation of endogenous retroelements by KRAB-ZFP proteins / Defective pyroptosis / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / HDACs deacetylate histones / Nonhomologous End-Joining (NHEJ) / RNA Polymerase I Promoter Escape / molecular condensate scaffold activity / Transcriptional regulation by small RNAs / Formation of the beta-catenin:TCF transactivating complex / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / NoRC negatively regulates rRNA expression / Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 / G2/M DNA damage checkpoint / HDMs demethylate histones / B-WICH complex positively regulates rRNA expression / DNA Damage/Telomere Stress Induced Senescence / heterochromatin formation / PKMTs methylate histone lysines / Metalloprotease DUBs / Meiotic recombination / Pre-NOTCH Transcription and Translation / RMTs methylate histone arginines / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / positive regulation of cellular senescence / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / UCH proteinases / antimicrobial humoral immune response mediated by antimicrobial peptide / nucleosome / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / antibacterial humoral response / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / site of double-strand break / RUNX1 regulates transcription of genes involved in differentiation of HSCs / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / Processing of DNA double-strand break ends / double-stranded DNA binding / Senescence-Associated Secretory Phenotype (SASP) / defense response to virus / Oxidative Stress Induced Senescence / Estrogen-dependent gene expression / chromosome, telomeric region / nuclear body / Ub-specific processing proteases / defense response to Gram-positive bacterium / protein heterodimerization activity / Amyloid fiber formation 類似検索 - 分子機能 | |||||||||
生物種 | Homo sapiens (ヒト) / Mus musculus (ハツカネズミ) | |||||||||
手法 | 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度: 6.8 Å | |||||||||
データ登録者 | Xu P / Li P | |||||||||
資金援助 | 米国, 2件
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引用 | ジャーナル: Nature / 年: 2020 タイトル: The molecular basis of tight nuclear tethering and inactivation of cGAS. 著者: Baoyu Zhao / Pengbiao Xu / Chesley M Rowlett / Tao Jing / Omkar Shinde / Yuanjiu Lei / A Phillip West / Wenshe Ray Liu / Pingwei Li / 要旨: Nucleic acids derived from pathogens induce potent innate immune responses. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor that catalyses the synthesis of the cyclic dinucleotide ...Nucleic acids derived from pathogens induce potent innate immune responses. Cyclic GMP-AMP synthase (cGAS) is a double-stranded DNA sensor that catalyses the synthesis of the cyclic dinucleotide cyclic GMP-AMP, which mediates the induction of type I interferons through the STING-TBK1-IRF3 signalling axis. cGAS was previously thought to not react with self DNA owing to its cytosolic localization; however, recent studies have shown that cGAS is localized mostly in the nucleus and has low activity as a result of tight nuclear tethering. Here we show that cGAS binds to nucleosomes with nanomolar affinity and that nucleosome binding potently inhibits its catalytic activity. To elucidate the molecular basis of cGAS inactivation by nuclear tethering, we determined the structure of mouse cGAS bound to human nucleosome by cryo-electron microscopy. The structure shows that cGAS binds to a negatively charged acidic patch formed by histones H2A and H2B via its second DNA-binding site. High-affinity nucleosome binding blocks double-stranded DNA binding and maintains cGAS in an inactive conformation. Mutations of cGAS that disrupt nucleosome binding alter cGAS-mediated signalling in cells. | |||||||||
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_22206.map.gz | 4 MB | EMDBマップデータ形式 | |
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ヘッダ (付随情報) | emd-22206-v30.xml emd-22206.xml | 20.7 KB 20.7 KB | 表示 表示 | EMDBヘッダ |
FSC (解像度算出) | emd_22206_fsc.xml | 7.8 KB | 表示 | FSCデータファイル |
画像 | emd_22206.png | 86.3 KB | ||
Filedesc metadata | emd-22206.cif.gz | 6.6 KB | ||
アーカイブディレクトリ | http://ftp.pdbj.org/pub/emdb/structures/EMD-22206 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-22206 | HTTPS FTP |
-検証レポート
文書・要旨 | emd_22206_validation.pdf.gz | 396.4 KB | 表示 | EMDB検証レポート |
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文書・詳細版 | emd_22206_full_validation.pdf.gz | 396 KB | 表示 | |
XML形式データ | emd_22206_validation.xml.gz | 10.1 KB | 表示 | |
CIF形式データ | emd_22206_validation.cif.gz | 13 KB | 表示 | |
アーカイブディレクトリ | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22206 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-22206 | 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_22206.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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注釈 | two mouse cGAS binds to reconstituted human nucleosome | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
投影像・断面図 | 画像のコントロール
画像は Spider により作成 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
ボクセルのサイズ | X=Y=Z: 1.07 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 : cGAS-nucleosome complex
+超分子 #1: cGAS-nucleosome complex
+超分子 #2: Histone
+超分子 #3: DNA
+超分子 #4: Cyclic GMP-AMP synthase
+分子 #1: Histone H3.2
+分子 #2: Histone H4
+分子 #3: Histone H2A type 1
+分子 #4: Histone H2B type 1-C/E/F/G/I
+分子 #7: Cyclic GMP-AMP synthase
+分子 #5: DNA (145-MER)
+分子 #6: DNA (145-MER)
+分子 #8: 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 | 0.4 mg/mL |
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緩衝液 | pH: 7.4 |
凍結 | 凍結剤: ETHANE / チャンバー内湿度: 100 % / チャンバー内温度: 298 K |
-電子顕微鏡法
顕微鏡 | FEI TITAN KRIOS |
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撮影 | フィルム・検出器のモデル: GATAN K2 SUMMIT (4k x 4k) 検出モード: COUNTING / 平均電子線量: 48.0 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 / Cs: 2.7 mm / 最大 デフォーカス(公称値): 1.8 µm 最小 デフォーカス(公称値): 0.7000000000000001 µm |
実験機器 | モデル: Titan Krios / 画像提供: FEI Company |