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リガンド : ACETATE IONリガンド : water 詳細 キーワード HDAC / Chromatin / Cell cycle / transcription / GENE REGULATION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
autosome / positive regulation of male mating behavior / protein de-2-hydroxyisobutyrylase activity / : / protein lysine delactylase activity / p75NTR negatively regulates cell cycle via SC1 / fungiform papilla formation / epidermal cell differentiation / eyelid development in camera-type eye / negative regulation of dendritic spine development ... autosome / positive regulation of male mating behavior / protein de-2-hydroxyisobutyrylase activity / : / protein lysine delactylase activity / p75NTR negatively regulates cell cycle via SC1 / fungiform papilla formation / epidermal cell differentiation / eyelid development in camera-type eye / negative regulation of dendritic spine development / histone decrotonylase activity / negative regulation of transcription initiation by RNA polymerase II / NuRD complex / positive regulation of interleukin-1 production / regulation of cell fate specification / EGR2 and SOX10-mediated initiation of Schwann cell myelination / negative regulation of stem cell population maintenance / regulation of stem cell differentiation / histone deacetylase activity, hydrolytic mechanism / histone deacetylase / XY body / ESC/E(Z) complex / positive regulation of intracellular estrogen receptor signaling pathway / cardiac muscle hypertrophy / behavioral response to ethanol / odontogenesis of dentin-containing tooth / cellular response to dopamine / STAT3 nuclear events downstream of ALK signaling / embryonic digit morphogenesis / histone deacetylase activity / protein lysine deacetylase activity / 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 / response to caffeine / Notch-HLH transcription pathway / Y chromosome / positive regulation of oligodendrocyte differentiation / X chromosome / histone deacetylase complex / positive regulation of stem cell population maintenance / dendrite development / Sin3-type complex / response to amyloid-beta / positive regulation of proteolysis / progesterone receptor signaling pathway / RNA Polymerase I Transcription Initiation / response to hyperoxia / hair follicle placode formation / cellular response to transforming growth factor beta stimulus / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / Regulation of MECP2 expression and activity / positive regulation of epithelial to mesenchymal transition / NF-kappaB binding / Transcriptional regulation of brown and beige adipocyte differentiation by EBF2 / cellular response to retinoic acid / Regulation of TP53 Activity through Acetylation / MECP2 regulates neuronal receptors and channels / Regulation of lipid metabolism by PPARalpha / heat shock protein binding / transcription repressor complex / response to amphetamine / negative regulation of cell migration / regulation of embryonic development / phosphatidylinositol binding / negative regulation of transforming growth factor beta receptor signaling pathway / Regulation of PTEN gene transcription / transcription corepressor binding / transcription coregulator binding / SUMOylation of chromatin organization proteins / response to cocaine / ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression / response to nicotine / circadian regulation of gene expression / Regulation of endogenous retroelements by KRAB-ZFP proteins / negative regulation of neuron projection development / HDACs deacetylate histones / Cytoprotection by HMOX1 / Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs) / promoter-specific chromatin binding / RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function / Negative Regulation of CDH1 Gene Transcription / NoRC negatively regulates rRNA expression / 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 / positive regulation of tumor necrosis factor production / transcription corepressor activity / cellular response to heat / histone binding / Factors involved in megakaryocyte development and platelet production / response to lipopolysaccharide / heterochromatin formation / Potential therapeutics for SARS / RNA polymerase II-specific DNA-binding transcription factor binding / chromosome, telomeric region / chromatin remodeling / response to xenobiotic stimulus / negative regulation of DNA-templated transcription / chromatin binding 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 / 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 ... PHD finger protein 12, MRG binding domain / PHD finger protein 12, MRG binding domain superfamily / PHD finger protein 12 / 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. / Histone deacetylase / 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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