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Open data
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Basic information
Entry | Database: PDB / ID: 8ffv | ||||||
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Title | Cryo-EM structure of the GR-Hsp90-FKBP52 complex | ||||||
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![]() | CHAPERONE / steroid hormone receptor / ligand binding / ATP binding / protein folding | ||||||
Function / homology | ![]() steroid hormone receptor complex assembly / negative regulation of microtubule polymerization or depolymerization / male sex differentiation / copper-dependent protein binding / Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / prostate gland development / steroid hormone binding / PTK6 Expression ...steroid hormone receptor complex assembly / negative regulation of microtubule polymerization or depolymerization / male sex differentiation / copper-dependent protein binding / Regulation of NPAS4 gene transcription / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / prostate gland development / steroid hormone binding / PTK6 Expression / neuroinflammatory response / copper ion transport / glucocorticoid metabolic process / microglia differentiation / nuclear glucocorticoid receptor binding / mammary gland duct morphogenesis / maternal behavior / protein-containing complex localization / 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 / negative regulation of microtubule polymerization / 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 / androgen receptor signaling pathway / 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 / 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 / embryo implantation Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.01 Å | ||||||
![]() | Noddings, C.M. / Agard, D.A. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Cryo-EM reveals how Hsp90 and FKBP immunophilins co-regulate the glucocorticoid receptor. Authors: Chari M Noddings / Jill L Johnson / David A Agard / ![]() Abstract: 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. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 739.3 KB | Display | ![]() |
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PDB format | ![]() | 612.5 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.4 MB | Display | ![]() |
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Full document | ![]() | 1.4 MB | Display | |
Data in XML | ![]() | 65.5 KB | Display | |
Data in CIF | ![]() | 99.4 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 29068MC ![]() 8ffwC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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1 |
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Components
-Protein , 3 types, 4 molecules ABCD
#1: Protein | Mass: 84650.531 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() References: UniProt: P07900, non-chaperonin molecular chaperone ATPase #2: Protein | | Mass: 41198.973 Da / Num. of mol.: 1 / Mutation: F602S Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | | Mass: 51876.520 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 3 types, 5 molecules ![](data/chem/img/ATP.gif)
![](data/chem/img/MG.gif)
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![](data/chem/img/MG.gif)
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#4: Chemical | #5: Chemical | #6: Chemical | ChemComp-DEX / | |
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-Details
Has ligand of interest | Y |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Complex of the Glucocorticoid Receptor ligand binding domain, Hsp90 alpha dimer, and the co-chaperone FKBP52 Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT |
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Molecular weight | Value: 0.307 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Specimen support | Grid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 105000 X / Nominal defocus max: 2000 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 5.9 sec. / Electron dose: 67 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 11162 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.01 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 307109 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | 3D fitting-ID: 1 / Source name: PDB / Type: experimental model
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