登録情報 データベース : EMDB / ID : EMD-16148 ダウンロードとリンクタイトル Cryo-EM structure of the human SIN3B histone deacetylase core complex at 2.8 Angstrom マップデータSIN3B-core complex map at 2.8 Angstrom 詳細 試料複合体 : SIN3B core complexタンパク質・ペプチド : Isoform 2 of Paired amphipathic helix protein Sin3bタンパク質・ペプチド : Histone deacetylase 2タンパク質・ペプチド : PHD finger protein 12リガンド : ZINC IONリガンド : CALCIUM ION カルシウムリガンド : ACETATE ION 酢酸塩リガンド : water 水 詳細 キーワード HDAC (ヒストン脱アセチル化酵素) / Chromatin (クロマチン) / Cell cycle (細胞周期) / transcription (転写 (生物学)) / GENE REGULATION (遺伝子発現の調節)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
常染色体 / protein de-2-hydroxyisobutyrylase activity / positive regulation of male mating behavior / negative regulation of peptidyl-lysine acetylation / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / negative regulation of dendritic spine development / histone decrotonylase activity / fungiform papilla formation / negative regulation of MHC class II biosynthetic process ... 常染色体 / protein de-2-hydroxyisobutyrylase activity / positive regulation of male mating behavior / negative regulation of peptidyl-lysine acetylation / p75NTR negatively regulates cell cycle via SC1 / epidermal cell differentiation / negative regulation of dendritic spine development / histone decrotonylase activity / fungiform papilla formation / negative regulation of MHC class II biosynthetic process / behavioral response to ethanol / positive regulation of interleukin-1 production / regulation of cell fate specification / negative regulation of stem cell population maintenance / EGR2 and SOX10-mediated initiation of Schwann cell myelination / negative regulation of transcription by competitive promoter binding / NuRD complex / regulation of stem cell differentiation / ESC/E(Z) complex / XY body / cellular response to dopamine / STAT3 nuclear events downstream of ALK signaling / ヒストン脱アセチル化酵素 / cardiac muscle hypertrophy / protein lysine deacetylase activity / positive regulation of signaling receptor activity / response to caffeine / 加水分解酵素; ペプチド以外のCN結合加水分解酵素; 鎖状アミドに作用 / histone deacetylase activity / embryonic digit morphogenesis / positive regulation of oligodendrocyte differentiation / positive regulation of stem cell population maintenance / Sin3-type complex / Notch-HLH transcription pathway / Y染色体 / dendrite development / eyelid development in camera-type eye / X染色体 / odontogenesis of dentin-containing tooth / RNA Polymerase I Transcription Initiation / response to amyloid-beta / positive regulation of proteolysis / histone deacetylase complex / hair follicle placode formation / Regulation of MECP2 expression and activity / NF-kappaB binding / positive regulation of collagen biosynthetic process / response to hyperoxia / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / heterochromatin formation / positive regulation of epithelial to mesenchymal transition / cellular response to retinoic acid / MECP2 regulates neuronal receptors and channels / positive regulation of tyrosine phosphorylation of STAT protein / Regulation of TP53 Activity through Acetylation / cellular response to transforming growth factor beta stimulus / heat shock protein binding / response to amphetamine / transcription repressor complex / Regulation of lipid metabolism by PPARalpha / SUMOylation of chromatin organization proteins / phosphatidylinositol binding / negative regulation of cell migration / transcription corepressor binding / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / response to cocaine / Regulation of PTEN gene transcription / HDACs deacetylate histones / promoter-specific chromatin binding / negative regulation of transforming growth factor beta receptor signaling pathway / response to nicotine / circadian regulation of gene expression / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / protein modification process / NoRC negatively regulates rRNA expression / negative regulation of DNA-binding transcription factor activity / Cytoprotection by HMOX1 / NOTCH1 Intracellular Domain Regulates Transcription / Constitutive Signaling by NOTCH1 PEST Domain Mutants / Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants / histone deacetylase binding / cellular response to hydrogen peroxide / transcription corepressor activity / positive regulation of tumor necrosis factor production / negative regulation of neuron projection development / cellular response to heat / Factors involved in megakaryocyte development and platelet production / histone binding / RNA polymerase II-specific DNA-binding transcription factor binding / Potential therapeutics for SARS / response to lipopolysaccharide / chromosome, telomeric region / クロマチンリモデリング / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / chromatin binding / クロマチン / positive regulation of cell population proliferation / negative regulation of apoptotic process / positive regulation of DNA-templated transcription 類似検索 - 分子機能 PHD finger protein 12, MRG binding domain / PHD finger protein 12, MRG binding domain superfamily / PHD finger protein 12 MRG binding domain / Histone deacetylase interacting domain / Sin3, C-terminal / Transcriptional regulatory protein Sin3-like / Sin3 family co-repressor / C-terminal domain of Sin3a protein / Histone deacetylase (HDAC) interacting / Paired amphipathic helix ... PHD finger protein 12, MRG binding domain / PHD finger protein 12, MRG binding domain superfamily / PHD finger protein 12 MRG binding domain / Histone deacetylase interacting domain / Sin3, C-terminal / Transcriptional regulatory protein Sin3-like / Sin3 family co-repressor / C-terminal domain of Sin3a protein / Histone deacetylase (HDAC) interacting / Paired amphipathic helix / Paired amphipathic helix superfamily / Paired amphipathic helix repeat / PAH domain profile. / ヒストン脱アセチル化酵素 / Forkhead-associated (FHA) domain profile. / Forkhead-associated (FHA) domain / Histone deacetylase family / Histone deacetylase domain / Histone deacetylase domain superfamily / Histone deacetylase domain / SMAD/FHA domain superfamily / Ureohydrolase domain superfamily / Zinc finger, PHD-type, conserved site / PHD-finger / Zinc finger PHD-type signature. / Zinc finger PHD-type profile. / Zinc finger, PHD-finger / Zinc finger, PHD-type / PHD zinc finger / Zinc finger, FYVE/PHD-type / Zinc finger, RING/FYVE/PHD-type 類似検索 - ドメイン・相同性 Paired amphipathic helix protein Sin3b / Histone deacetylase 2 / PHD finger protein 12 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 : 2.8 Å 詳細 データ登録者Wan MSM / Muhammad R / Koliopolous MG / Alfieri C 資金援助 英国, 1件 詳細 詳細を隠すOrganization Grant number 国 Wellcome Trust 215458/Z/19/Z 英国
引用ジャーナル : Nat Commun / 年 : 2023タイトル : Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex.著者 : Mandy S M Wan / Reyhan Muhammad / Marios G Koliopoulos / Theodoros I Roumeliotis / Jyoti S Choudhary / Claudio Alfieri / 要旨 : Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing ... Lysine acetylation in histone tails is a key post-translational modification that controls transcription activation. Histone deacetylase complexes remove histone acetylation, thereby repressing transcription and regulating the transcriptional output of each gene. Although these complexes are drug targets and crucial regulators of organismal physiology, their structure and mechanisms of action are largely unclear. Here, we present the structure of a complete human SIN3B histone deacetylase holo-complex with and without a substrate mimic. Remarkably, SIN3B encircles the deacetylase and contacts its allosteric basic patch thereby stimulating catalysis. A SIN3B loop inserts into the catalytic tunnel, rearranges to accommodate the acetyl-lysine moiety, and stabilises the substrate for specific deacetylation, which is guided by a substrate receptor subunit. Our findings provide a model of specificity for a main transcriptional regulator conserved from yeast to human and a resource of protein-protein interactions for future drug designs. 履歴 登録 2022年11月16日 - ヘッダ(付随情報) 公開 2023年5月10日 - マップ公開 2023年5月10日 - 更新 2024年3月27日 - 現状 2024年3月27日 処理サイト : PDBe / 状態 : 公開
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