登録情報 データベース : PDB / ID : 7kw7 構造の表示 ダウンロードとリンクタイトル Atomic cryoEM structure of Hsp90-Hsp70-Hop-GR 要素Glucocorticoid receptor Heat shock 70 kDa protein 1A Heat shock protein HSP 90-alpha Stress-induced-phosphoprotein 1 詳細キーワード CHAPERONE / Client-loading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
positive regulation of endoribonuclease activity / denatured protein binding / Regulation of NPAS4 gene transcription / cellular heat acclimation / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / death receptor agonist activity / negative regulation of inclusion body assembly / Viral RNP Complexes in the Host Cell Nucleus / positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway ... positive regulation of endoribonuclease activity / denatured protein binding / Regulation of NPAS4 gene transcription / cellular heat acclimation / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / death receptor agonist activity / negative regulation of inclusion body assembly / Viral RNP Complexes in the Host Cell Nucleus / positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway / C3HC4-type RING finger domain binding / steroid hormone binding / PTK6 Expression / positive regulation of microtubule nucleation / dynein axonemal particle / ATP-dependent protein disaggregase activity / neuroinflammatory response / glucocorticoid metabolic process / microglia differentiation / misfolded protein binding / mammary gland duct morphogenesis / maternal behavior / regulation of mitotic spindle assembly / negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway / positive regulation of tumor necrosis factor-mediated signaling pathway / astrocyte differentiation / cellular response to interleukin-7 / transcription regulator inhibitor activity / cellular response to glucocorticoid stimulus / aggresome / protein folding chaperone complex / RND1 GTPase cycle / motor behavior / positive regulation of tau-protein kinase activity / sperm mitochondrial sheath / dATP binding / Scavenging by Class F Receptors / sulfonylurea receptor binding / lysosomal transport / CTP binding / positive regulation of protein polymerization / vRNP Assembly / UTP binding / sperm plasma membrane / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / adrenal gland development / protein insertion into mitochondrial outer membrane / regulation of gluconeogenesis / cellular response to steroid hormone stimulus / Respiratory syncytial virus genome replication / Rho GDP-dissociation inhibitor binding / Uptake and function of diphtheria toxin / 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 / dendritic growth cone / mRNA catabolic process / regulation of postsynaptic membrane neurotransmitter receptor levels / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / chaperone cofactor-dependent protein refolding / skeletal muscle contraction / Signaling by ERBB2 / telomere maintenance via telomerase / HSF1-dependent transactivation / positive regulation of cell size / response to unfolded protein / protein unfolding / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / chaperone-mediated protein complex assembly / Regulation of HSF1-mediated heat shock response / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / cellular response to unfolded protein / RHOBTB2 GTPase cycle / estrogen response element binding / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / cellular response to dexamethasone stimulus / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / eNOS activation / axonal growth cone / positive regulation of lamellipodium assembly / DNA polymerase binding / nuclear receptor-mediated steroid hormone signaling pathway / core promoter sequence-specific DNA binding / ATP metabolic process 類似検索 - 分子機能 STI1/HOP, DP domain / STI1/HOP, DP domain / Tetratricopeptide repeat 2 / Tetratricopeptide repeat / Glucocorticoid receptor / Glucocorticoid receptor / Heat shock chaperonin-binding / Heat shock chaperonin-binding motif. / TPR repeat / Tetratricopeptide repeat ... STI1/HOP, DP domain / STI1/HOP, DP domain / Tetratricopeptide repeat 2 / Tetratricopeptide repeat / Glucocorticoid receptor / Glucocorticoid receptor / Heat shock chaperonin-binding / Heat shock chaperonin-binding motif. / TPR repeat / Tetratricopeptide repeat / Heat shock hsp70 proteins family signature 2. / Heat shock hsp70 proteins family signature 1. / Heat shock hsp70 proteins family signature 3. / Heat shock protein 70, conserved site / Heat shock protein 70kD, peptide-binding domain superfamily / Heat shock protein 70 family / Hsp70 protein / Heat shock protein 70kD, C-terminal domain superfamily / 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 / Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase / : / TPR repeat region circular profile. / TPR repeat profile. / Tetratricopeptide repeats / Tetratricopeptide repeat / Histidine kinase-like ATPases / Histidine kinase/HSP90-like ATPase / Nuclear hormone receptor / Histidine kinase/HSP90-like ATPase superfamily / 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 / Nuclear receptor (NR) ligand-binding (LBD) domain profile. / Ligand binding domain of hormone receptors / Zinc finger, NHR/GATA-type / ATPase, nucleotide binding domain / Ligand-binding domain of nuclear hormone receptor / Tetratricopeptide-like helical domain superfamily / Ribosomal protein S5 domain 2-type fold 類似検索 - ドメイン・相同性 ADENOSINE-5'-DIPHOSPHATE / : / Glucocorticoid receptor / Heat shock protein HSP 90-alpha / Heat shock 70 kDa protein 1A / Stress-induced-phosphoprotein 1 類似検索 - 構成要素生物種 Homo sapiens (ヒト)手法 電子顕微鏡法 / 単粒子再構成法 / クライオ電子顕微鏡法 / 解像度 : 3.57 Å 詳細データ登録者 Wang, R.Y. / Noddings, C.M. / Kirschke, E. / Myasnikov, A. / Johnson, J.L. / Agard, D.A. 資金援助 米国, 1件 詳細 詳細を隠す組織 認可番号 国 Howard Hughes Medical Institute (HHMI) 米国
引用ジャーナル : Nature / 年 : 2022タイトル : Structure of Hsp90-Hsp70-Hop-GR reveals the Hsp90 client-loading mechanism.著者 : Ray Yu-Ruei Wang / Chari M Noddings / Elaine Kirschke / Alexander G Myasnikov / Jill L Johnson / David A Agard / 要旨 : Maintaining a healthy proteome is fundamental for the survival of all organisms. Integral to this are Hsp90 and Hsp70, molecular chaperones that together facilitate the folding, remodelling and ... Maintaining a healthy proteome is fundamental for the survival of all organisms. Integral to this are Hsp90 and Hsp70, molecular chaperones that together facilitate the folding, remodelling and maturation of the many 'client proteins' of Hsp90. The glucocorticoid receptor (GR) is a model client protein that is strictly dependent on Hsp90 and Hsp70 for activity. Chaperoning GR involves a cycle of inactivation by Hsp70; formation of an inactive GR-Hsp90-Hsp70-Hop 'loading' complex; conversion to an active GR-Hsp90-p23 'maturation' complex; and subsequent GR release. However, to our knowledge, a molecular understanding of this intricate chaperone cycle is lacking for any client protein. Here we report the cryo-electron microscopy structure of the GR-loading complex, in which Hsp70 loads GR onto Hsp90, uncovering the molecular basis of direct coordination by Hsp90 and Hsp70. The structure reveals two Hsp70 proteins, one of which delivers GR and the other scaffolds the Hop cochaperone. Hop interacts with all components of the complex, including GR, and poises Hsp90 for subsequent ATP hydrolysis. GR is partially unfolded and recognized through an extended binding pocket composed of Hsp90, Hsp70 and Hop, revealing the mechanism of GR loading and inactivation. Together with the GR-maturation complex structure, we present a complete molecular mechanism of chaperone-dependent client remodelling, and establish general principles of client recognition, inhibition, transfer and activation. 履歴 登録 2020年11月30日 登録サイト : RCSB / 処理サイト : RCSB改定 1.0 2021年12月8日 Provider : repository / タイプ : Initial release改定 1.1 2022年1月26日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.country / _citation.journal_abbrev ... _citation.country / _citation.journal_abbrev / _citation.journal_id_ASTM / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation.year / _citation_author.identifier_ORCID / _citation_author.name 改定 1.2 2022年2月2日 Group : Database references / カテゴリ : citation / citation_authorItem : _citation.journal_volume / _citation.page_first ... _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.year / _citation_author.identifier_ORCID 改定 1.3 2024年5月29日 Group : Data collection / カテゴリ : chem_comp_atom / chem_comp_bond
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