登録情報 データベース : EMDB / ID : EMD-23054 構造の表示 ダウンロードとリンクタイトル Focused map of the Hsp90-Hsp70-Hop-GR complex: Hsp90B-NTD-MD:Hsp70D-NBD マップデータFocused map of the Hsp90-Hsp70-Hop-GR complex: Hsp90B-NTD-MD:Hsp70D-NBD 詳細 試料複合体 : Hsp90-Hsp70-Hop-GR complex 詳細機能・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 / cellular heat acclimation / 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 / positive regulation of microtubule nucleation / ATP-dependent protein disaggregase activity ... positive regulation of endoribonuclease activity / denatured protein binding / cellular heat acclimation / 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 / positive regulation of microtubule nucleation / ATP-dependent protein disaggregase activity / misfolded protein binding / 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 / transcription regulator inhibitor activity / aggresome / 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 / positive regulation of tau-protein kinase activity / chaperone-mediated autophagy / telomerase holoenzyme complex assembly / protein insertion into mitochondrial outer membrane / 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 / regulation of postsynaptic membrane neurotransmitter receptor levels / dendritic growth cone / mRNA catabolic process / Sema3A PAK dependent Axon repulsion / regulation of protein ubiquitination / skeletal muscle contraction / chaperone cofactor-dependent protein refolding / HSF1-dependent transactivation / positive regulation of cell size / response to unfolded protein / telomere maintenance via telomerase / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / chaperone-mediated protein complex assembly / Regulation of HSF1-mediated heat shock response / protein unfolding / HSF1 activation / regulation of protein-containing complex assembly / Attenuation phase / cellular response to unfolded protein / RHOBTB2 GTPase cycle / negative regulation of endoplasmic reticulum stress-induced intrinsic apoptotic signaling pathway / eNOS activation / axonal growth cone / positive regulation of lamellipodium assembly / DNA polymerase binding / ATP metabolic process / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / protein folding chaperone / inclusion body / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / Recruitment of mitotic centrosome proteins and complexes / : / Signaling by ERBB2 / cardiac muscle cell apoptotic process / negative regulation of protein ubiquitination / positive regulation of defense response to virus by host / endocytic vesicle lumen / positive regulation of cardiac muscle contraction / 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 / activation of innate immune response / centriole / nitric-oxide synthase regulator activity / positive regulation of interferon-beta production / response to cold / Constitutive Signaling by Overexpressed ERBB2 / AURKA Activation by TPX2 類似検索 - 分子機能 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 / Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. ... 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 / 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 / Histidine kinase-like ATPases / Histidine kinase/HSP90-like ATPase / Histidine kinase/HSP90-like ATPase superfamily / ATPase, nucleotide binding domain / Ribosomal protein S5 domain 2-type fold 類似検索 - ドメイン・相同性 Heat shock protein HSP 90-alpha / Heat shock 70 kDa protein 1A 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 : 3.53 Å 詳細 データ登録者Wang RY / Agard DA 資金援助 米国, 1件 詳細 詳細を隠すOrganization Grant number 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12月1日 - ヘッダ(付随情報) 公開 2021年12月8日 - マップ公開 2021年12月8日 - 更新 2022年2月2日 - 現状 2022年2月2日 処理サイト : RCSB / 状態 : 公開
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