登録情報 データベース : EMDB / ID : EMD-30339 構造の表示 ダウンロードとリンクタイトル Structure of the 1:1 cGAS-nucleosome complex マップデータ 詳細 試料複合体 : the cGAS-nucleosome complex in 1:1 molar ratioタンパク質・ペプチド : Histone H3.1タンパク質・ペプチド : Histone H4タンパク質・ペプチド : Histone H2A type 1-B/Eタンパク質・ペプチド : Histone H2B type 1-Jタンパク質・ペプチド : Cyclic GMP-AMP synthaseDNA : DNA (147-MER)DNA : DNA (147-MER) 残り3件を表示 表示を減らす 詳細 キーワード cGAS / nucleosome / inhibition / cryo-EM / IMMUNE SYSTEM / STRUCTURAL PROTEIN-TRANSFERASE-DNA complex機能・相同性 機能・相同性情報分子機能 ドメイン・相同性 構成要素
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 / heterochromatin organization / negative regulation of tumor necrosis factor-mediated signaling pathway / positive regulation of type I interferon production / negative regulation of megakaryocyte differentiation / protein localization to CENP-A containing chromatin / negative regulation of double-strand break repair via homologous recombination / Chromatin modifying enzymes / Replacement of protamines by nucleosomes in the male pronucleus / CENP-A containing nucleosome / epigenetic regulation of gene expression / Packaging Of Telomere Ends / Recognition and association of DNA glycosylase with site containing an affected purine / Cleavage of the damaged purine / nucleosome binding / nucleosomal DNA binding / Deposition of new CENPA-containing nucleosomes at the centromere / positive regulation of defense response to virus by host / Recognition and association of DNA glycosylase with site containing an affected pyrimidine / Cleavage of the damaged pyrimidine / Inhibition of DNA recombination at telomere / Meiotic synapsis / phosphatidylinositol-4,5-bisphosphate binding / telomere organization / activation of innate immune response / RNA Polymerase I Promoter Opening / Interleukin-7 signaling / Assembly of the ORC complex at the origin of replication / SUMOylation of chromatin organization proteins / cAMP-mediated signaling / DNA methylation / Condensation of Prophase Chromosomes / SIRT1 negatively regulates rRNA expression / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / Chromatin modifications during the maternal to zygotic transition (MZT) / HCMV Late Events / innate immune response in mucosa / molecular condensate scaffold activity / PRC2 methylates histones and DNA / Defective pyroptosis / HDACs deacetylate histones / determination of adult lifespan / RNA Polymerase I Promoter Escape / lipopolysaccharide binding / Nonhomologous End-Joining (NHEJ) / 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 / Metalloprotease DUBs / PKMTs methylate histone lysines / Meiotic recombination / RMTs methylate histone arginines / Pre-NOTCH Transcription and Translation / Activation of anterior HOX genes in hindbrain development during early embryogenesis / HCMV Early Events / Transcriptional regulation of granulopoiesis / structural constituent of chromatin / antimicrobial humoral immune response mediated by antimicrobial peptide / positive regulation of cellular senescence / UCH proteinases / nucleosome / nucleosome assembly / E3 ubiquitin ligases ubiquitinate target proteins / Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks / chromatin organization / RUNX1 regulates transcription of genes involved in differentiation of HSCs / site of double-strand break / Factors involved in megakaryocyte development and platelet production / HATs acetylate histones / gene expression / Processing of DNA double-strand break ends / antibacterial humoral response / Senescence-Associated Secretory Phenotype (SASP) / double-stranded DNA binding / Oxidative Stress Induced Senescence / defense response to Gram-negative bacterium / defense response to virus / Estrogen-dependent gene expression / killing of cells of another organism / chromosome, telomeric region / nuclear body / Ub-specific processing proteases 類似検索 - 分子機能 Mab-21-like, nucleotidyltransferase domain / Mab-21-like, HhH/H2TH-like domain / Mab-21 protein HhH/H2TH-like domain / Mab-21 protein nucleotidyltransferase domain / Mab-21-like / Mab-21 / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site ... Mab-21-like, nucleotidyltransferase domain / Mab-21-like, HhH/H2TH-like domain / Mab-21 protein HhH/H2TH-like domain / Mab-21 protein nucleotidyltransferase domain / Mab-21-like / Mab-21 / Histone H2B signature. / Histone H2B / Histone H2B / Histone H2A conserved site / Histone H2A signature. / Histone H2A, C-terminal domain / C-terminus of histone H2A / Histone H2A / Histone 2A / Histone H4, conserved site / Histone H4 signature. / Histone H4 / Histone H4 / TATA box binding protein associated factor / TATA box binding protein associated factor (TAF), histone-like fold domain / CENP-T/Histone H4, histone fold / Centromere kinetochore component CENP-T histone fold / Histone H3 signature 1. / Histone H3 signature 2. / Histone H3 / Histone H3/CENP-A / Histone H2A/H2B/H3 / Core histone H2A/H2B/H3/H4 / Histone-fold 類似検索 - ドメイン・相同性 Histone H2A type 1-B/E / Histone H2B type 1-J / Histone H4 / Histone H3.1 / Cyclic GMP-AMP synthase 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.8 Å 詳細 データ登録者Cao D / Han X 資金援助 中国, 7件 詳細 詳細を隠すOrganization Grant number 国 Ministry of Science and Technology (MoST, China) 2017YFA0504700 中国 Ministry of Science and Technology (MoST, China) 2019YFA0508900 中国 National Natural Science Foundation of China (NSFC) 31930069 中国 National Natural Science Foundation of China (NSFC) 31521002 中国 National Natural Science Foundation of China (NSFC) 31991162 中国 Chinese Academy of Sciences XDB37040101 中国 Chinese Academy of Sciences XDB37010101 中国
引用ジャーナル : Cell Res / 年 : 2020タイトル : Structural basis for nucleosome-mediated inhibition of cGAS activity.著者 : Duanfang Cao / Xiaonan Han / Xiaoyi Fan / Rui-Ming Xu / Xinzheng Zhang / 要旨 : Activation of cyclic GMP-AMP synthase (cGAS) through sensing cytosolic double stranded DNA (dsDNA) plays a pivotal role in innate immunity against exogenous infection as well as cellular regulation ... Activation of cyclic GMP-AMP synthase (cGAS) through sensing cytosolic double stranded DNA (dsDNA) plays a pivotal role in innate immunity against exogenous infection as well as cellular regulation under stress. Aberrant activation of cGAS induced by self-DNA is related to autoimmune diseases. cGAS accumulates at chromosomes during mitosis or spontaneously in the nucleus. Binding of cGAS to the nucleosome competitively attenuates the dsDNA-mediated cGAS activation, but the molecular mechanism of the attenuation is still poorly understood. Here, we report two cryo-electron microscopy structures of cGAS-nucleosome complexes. The structures reveal that cGAS interacts with the nucleosome as a monomer, forming 1:1 and 2:2 complexes, respectively. cGAS contacts the nucleosomal acidic patch formed by the H2A-H2B heterodimer through the dsDNA-binding site B in both complexes, and could interact with the DNA from the other symmetrically placed nucleosome via the dsDNA-binding site C in the 2:2 complex. The bound nucleosome inhibits the activation of cGAS through blocking the interaction of cGAS with ligand dsDNA and disrupting cGAS dimerization. R236A or R255A mutation of cGAS impairs the binding between cGAS and the nucleosome, and largely relieves the nucleosome-mediated inhibition of cGAS activity. Our study provides structural insights into the inhibition of cGAS activity by the nucleosome, and advances the understanding of the mechanism by which hosts avoid the autoimmune attack caused by cGAS. 履歴 登録 2020年6月17日 - ヘッダ(付随情報) 公開 2020年10月7日 - マップ公開 2020年10月7日 - 更新 2024年3月27日 - 現状 2024年3月27日 処理サイト : PDBj / 状態 : 公開
すべて表示 表示を減らす