登録情報 データベース : EMDB / ID : EMD-29069 ダウンロードとリンクタイトル Cryo-EM structure of the GR-Hsp90-FKBP51 complex マップデータSharpened consensus map for the GR-Hsp90-FKBP51 complex 詳細 試料複合体 : Complex of the Glucocorticoid Receptor ligand binding domain, Hsp90 alpha dimer, and the co-chaperone FKBP51タンパク質・ペプチド : Heat shock protein HSP 90-alphaタンパク質・ペプチド : Glucocorticoid receptorタンパク質・ペプチド : Peptidyl-prolyl cis-trans isomerase FKBP5リガンド : ADENOSINE-5'-TRIPHOSPHATEリガンド : MAGNESIUM IONリガンド : DEXAMETHASONE 詳細 キーワード chaperone / steroid hormone receptor / ligand binding / ATP binding / protein folding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
Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / steroid hormone binding / PTK6 Expression / neuroinflammatory response / glucocorticoid metabolic process / microglia differentiation / mammary gland duct morphogenesis / maternal behavior ... Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / steroid hormone binding / PTK6 Expression / neuroinflammatory response / glucocorticoid metabolic process / microglia differentiation / mammary gland duct morphogenesis / maternal behavior / astrocyte differentiation / cellular response to glucocorticoid stimulus / motor behavior / sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / positive regulation of tau-protein kinase activity / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / regulation of gluconeogenesis / adrenal gland development / protein insertion into mitochondrial outer membrane / cellular response to steroid hormone stimulus / Respiratory syncytial virus genome replication / Uptake and function of diphtheria toxin / Rho GDP-dissociation inhibitor binding / FK506 binding / mitochondrial transport / Drug-mediated inhibition of ERBB2 signaling / Resistance of ERBB2 KD mutants to trastuzumab / Resistance of ERBB2 KD mutants to sapitinib / Resistance of ERBB2 KD mutants to tesevatinib / Resistance of ERBB2 KD mutants to neratinib / Resistance of ERBB2 KD mutants to osimertinib / Resistance of ERBB2 KD mutants to afatinib / Resistance of ERBB2 KD mutants to AEE788 / Resistance of ERBB2 KD mutants to lapatinib / Drug resistance in ERBB2 TMD/JMD mutants / PIWI-interacting RNA (piRNA) biogenesis / TPR domain binding / non-chaperonin molecular chaperone ATPase / Assembly and release of respiratory syncytial virus (RSV) virions / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / skeletal muscle contraction / HSF1-dependent transactivation / positive regulation of cell size / response to unfolded protein / telomere maintenance via telomerase / chaperone-mediated protein complex assembly / protein unfolding / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / RHOBTB2 GTPase cycle / estrogen response element binding / eNOS activation / axonal growth cone / positive regulation of lamellipodium assembly / DNA polymerase binding / chaperone-mediated protein folding / nuclear receptor-mediated steroid hormone signaling pathway / MECP2 regulates neuronal receptors and channels / core promoter sequence-specific DNA binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / positive regulation of telomerase activity / positive regulation of cardiac muscle contraction / Signaling by ERBB2 / cardiac muscle cell apoptotic process / positive regulation of defense response to virus by host / cellular response to transforming growth factor beta stimulus / endocytic vesicle lumen / Recruitment of NuMA to mitotic centrosomes / response to salt stress / Anchoring of the basal body to the plasma membrane / heat shock protein binding / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / TBP-class protein binding / activation of innate immune response / nitric-oxide synthase regulator activity / steroid binding / positive regulation of interferon-beta production / response to cold / Constitutive Signaling by Overexpressed ERBB2 / AURKA Activation by TPX2 / lysosomal lumen / ESR-mediated signaling / cellular response to dexamethasone stimulus 類似検索 - 分子機能 Glucocorticoid receptor / Glucocorticoid receptor / Tetratricopeptide repeat / Tetratricopeptide repeat 1 / Tetratricopeptide repeat / Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat shock protein Hsp90 family ... Glucocorticoid receptor / Glucocorticoid receptor / Tetratricopeptide repeat / Tetratricopeptide repeat 1 / Tetratricopeptide repeat / Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. / HSP90, C-terminal domain / Heat shock protein Hsp90, N-terminal / Heat shock protein Hsp90 family / Hsp90 protein / FKBP-type peptidyl-prolyl cis-trans isomerase domain profile. / FKBP-type peptidyl-prolyl cis-trans isomerase domain / FKBP-type peptidyl-prolyl cis-trans isomerase / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / Peptidyl-prolyl cis-trans isomerase domain superfamily / TPR repeat region circular profile. / TPR repeat profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Histidine kinase-like ATPases / Histidine kinase/HSP90-like ATPase / Histidine kinase/HSP90-like ATPase superfamily / Nuclear hormone receptor / Nuclear hormones receptors DNA-binding region signature. / Zinc finger, nuclear hormone receptor-type / Zinc finger, C4 type (two domains) / Nuclear hormone receptors DNA-binding domain profile. / c4 zinc finger in nuclear hormone receptors / Nuclear hormone receptor, ligand-binding domain / Nuclear hormone receptor-like domain superfamily / Ligand-binding domain of nuclear hormone receptor / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type / Tetratricopeptide-like helical domain superfamily / Ribosomal protein S5 domain 2-type fold 類似検索 - ドメイン・相同性 Glucocorticoid receptor / Heat shock protein HSP 90-alpha / Peptidyl-prolyl cis-trans isomerase FKBP5 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 : 3.23 Å 詳細 データ登録者Noddings CM / Agard DA 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 国 National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) GM118099 米国
引用ジャーナル : Nat Struct Mol Biol / 年 : 2023タイトル : Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor.著者 : Chari M Noddings / Jill L Johnson / David A Agard / 要旨 : Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins, including the glucocorticoid receptor (GR). Previously, we revealed that Hsp70 ... Hsp90 is an essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins, including the glucocorticoid receptor (GR). Previously, we revealed that Hsp70 and Hsp90 remodel the conformation of GR to regulate ligand binding, aided by co-chaperones. In vivo, the co-chaperones FKBP51 and FKBP52 antagonistically regulate GR activity, but a molecular understanding is lacking. Here we present a 3.01 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP52 complex, revealing how FKBP52 integrates into the GR chaperone cycle and directly binds to the active client, potentiating GR activity in vitro and in vivo. We also present a 3.23 Å cryogenic electron microscopy structure of the human GR:Hsp90:FKBP51 complex, revealing how FKBP51 competes with FKBP52 for GR:Hsp90 binding and demonstrating how FKBP51 can act as a potent antagonist to FKBP52. Altogether, we demonstrate how FKBP51 and FKBP52 integrate into the GR chaperone cycle to advance GR to the next stage of maturation. 履歴 登録 2022年12月10日 - ヘッダ(付随情報) 公開 2023年11月1日 - マップ公開 2023年11月1日 - 更新 2023年12月20日 - 現状 2023年12月20日 処理サイト : RCSB / 状態 : 公開
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