[English] 日本語
Yorodumi
- PDB-7krj: The GR-Maturation Complex: Glucocorticoid Receptor in complex wit... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7krj
TitleThe GR-Maturation Complex: Glucocorticoid Receptor in complex with Hsp90 and co-chaperone p23
Components
  • Glucocorticoid receptor
  • Heat shock protein HSP 90-alpha
  • Prostaglandin E synthase 3
KeywordsCHAPERONE / ligand binding / ATP binding / protein folding / cryo-EM
Function / homology
Function and homology information


lung saccule development / prostaglandin-E synthase / prostaglandin-E synthase activity / Regulation of NPAS4 gene transcription / nuclear receptor-mediated glucocorticoid signaling pathway / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / Aryl hydrocarbon receptor signalling / steroid hormone binding / PTK6 Expression ...lung saccule development / prostaglandin-E synthase / prostaglandin-E synthase activity / Regulation of NPAS4 gene transcription / nuclear receptor-mediated glucocorticoid signaling pathway / regulation of glucocorticoid biosynthetic process / nuclear glucocorticoid receptor activity / Aryl hydrocarbon receptor signalling / steroid hormone binding / PTK6 Expression / glucocorticoid metabolic process / neuroinflammatory response / Synthesis of Prostaglandins (PG) and Thromboxanes (TX) / cyclooxygenase pathway / mammary gland duct morphogenesis / microglia differentiation / astrocyte differentiation / maternal behavior / glycogen biosynthetic process / telomerase holoenzyme complex / protein folding chaperone complex / prostaglandin biosynthetic process / cellular response to glucocorticoid stimulus / motor behavior / adrenal gland development / regulation of gluconeogenesis / sperm mitochondrial sheath / sulfonylurea receptor binding / dATP binding / cellular response to steroid hormone stimulus / CTP binding / positive regulation of protein polymerization / vRNP Assembly / Scavenging by Class F Receptors / UTP binding / skin development / sperm plasma membrane / chaperone-mediated autophagy / Respiratory syncytial virus genome replication / Rho GDP-dissociation inhibitor binding / telomerase holoenzyme complex assembly / mitochondrial transport / protein insertion into mitochondrial outer membrane / Uptake and function of diphtheria toxin / 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 / TPR domain binding / non-chaperonin molecular chaperone ATPase / PIWI-interacting RNA (piRNA) biogenesis / Assembly and release of respiratory syncytial virus (RSV) virions / dendritic growth cone / : / Sema3A PAK dependent Axon repulsion / skeletal muscle contraction / protein unfolding / regulation of postsynaptic membrane neurotransmitter receptor levels / positive regulation of cell size / regulation of protein ubiquitination / estrogen response element binding / HSF1-dependent transactivation / response to unfolded protein / HSF1 activation / regulation of protein-containing complex assembly / FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes / telomere maintenance via telomerase / nuclear receptor-mediated steroid hormone signaling pathway / chaperone-mediated protein complex assembly / Attenuation phase / neurofibrillary tangle assembly / RHOBTB2 GTPase cycle / core promoter sequence-specific DNA binding / axonal growth cone / positive regulation of lamellipodium assembly / eNOS activation / cellular response to transforming growth factor beta stimulus / DNA polymerase binding / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / positive regulation of defense response to virus by host / Signaling by ERBB2 / steroid binding / response to salt stress / cardiac muscle cell apoptotic process / TBP-class protein binding / positive regulation of telomere maintenance via telomerase / endocytic vesicle lumen / telomere maintenance / Loss of Nlp from mitotic centrosomes / Loss of proteins required for interphase microtubule organization from the centrosome / positive regulation of cardiac muscle contraction / nitric-oxide synthase regulator activity / Recruitment of mitotic centrosome proteins and complexes / cellular response to dexamethasone stimulus
Similarity search - Function
Co-chaperone protein p23-like / CS domain / CS domain / CS domain profile. / Immunoglobulin-like - #790 / Glucocorticoid receptor / Glucocorticoid receptor / HSP20-like chaperone / Heat shock protein Hsp90, conserved site / Heat shock hsp90 proteins family signature. ...Co-chaperone protein p23-like / CS domain / CS domain / CS domain profile. / Immunoglobulin-like - #790 / Glucocorticoid receptor / Glucocorticoid receptor / HSP20-like chaperone / 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 / : / Retinoid X Receptor / Retinoid X Receptor / 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 / Double treble clef zinc finger, C4 type / 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 / Ribosomal protein S5 domain 2-type fold / Immunoglobulin-like / Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
ADENOSINE-5'-TRIPHOSPHATE / DEXAMETHASONE / Glucocorticoid receptor / Heat shock protein HSP 90-alpha / Prostaglandin E synthase 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.56 Å
AuthorsNoddings, C.M. / Wang, Y.-R. / Agard, D.A.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R35GM118099 United States
CitationJournal: Nature / Year: 2022
Title: Structure of Hsp90-p23-GR reveals the Hsp90 client-remodelling mechanism.
Authors: Chari M Noddings / Ray Yu-Ruei Wang / Jill L Johnson / David A Agard /
Abstract: Hsp90 is a conserved and essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins. The glucocorticoid receptor (GR) is a model client that constantly ...Hsp90 is a conserved and essential molecular chaperone responsible for the folding and activation of hundreds of 'client' proteins. The glucocorticoid receptor (GR) is a model client that constantly depends on Hsp90 for activity. GR ligand binding was previously shown to nr inhibited by Hsp70 and restored by Hsp90, aided by the co-chaperone p23. However, a molecular understanding of the chaperone-mediated remodelling that occurs between the inactive Hsp70-Hsp90 'client-loading complex' and an activated Hsp90-p23 'client-maturation complex' is lacking for any client, including GR. Here we present a cryo-electron microscopy (cryo-EM) structure of the human GR-maturation complex (GR-Hsp90-p23), revealing that the GR ligand-binding domain is restored to a folded, ligand-bound conformation, while being simultaneously threaded through the Hsp90 lumen. In addition, p23 directly stabilizes native GR using a C-terminal helix, resulting in enhanced ligand binding. This structure of a client bound to Hsp90 in a native conformation contrasts sharply with the unfolded kinase-Hsp90 structure. Thus, aided by direct co-chaperone-client interactions, Hsp90 can directly dictate client-specific folding outcomes. Together with the GR-loading complex structure, we present the molecular mechanism of chaperone-mediated GR remodelling, establishing the first, to our knowledge, complete chaperone cycle for any Hsp90 client.
History
DepositionNov 20, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 12, 2022Provider: repository / Type: Initial release
Revision 1.1Jan 26, 2022Group: Database references / Category: citation
Item: _citation.journal_volume / _citation.page_first / _citation.page_last
Revision 1.2May 29, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / em_3d_fitting_list / pdbx_initial_refinement_model
Item: _em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id ..._em_3d_fitting_list.accession_code / _em_3d_fitting_list.initial_refinement_model_id / _em_3d_fitting_list.source_name / _em_3d_fitting_list.type

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-23004
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Heat shock protein HSP 90-alpha
B: Heat shock protein HSP 90-alpha
C: Prostaglandin E synthase 3
D: Glucocorticoid receptor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)219,6649
Polymers218,2094
Non-polymers1,4555
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 3 types, 4 molecules ABCD

#1: Protein Heat shock protein HSP 90-alpha / Heat shock 86 kDa / HSP86 / Lipopolysaccharide-associated protein 2 / LPS-associated protein 2 / ...Heat shock 86 kDa / HSP86 / Lipopolysaccharide-associated protein 2 / LPS-associated protein 2 / Renal carcinoma antigen NY-REN-38


Mass: 84781.727 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HSP90AA1, HSP90A, HSPC1, HSPCA / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P07900
#2: Protein Prostaglandin E synthase 3 / Cytosolic prostaglandin E2 synthase / cPGES / Hsp90 co-chaperone / Progesterone receptor complex ...Cytosolic prostaglandin E2 synthase / cPGES / Hsp90 co-chaperone / Progesterone receptor complex p23 / Telomerase-binding protein p23


Mass: 18720.395 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PTGES3, P23, TEBP / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: Q15185, prostaglandin-E synthase
#3: Protein Glucocorticoid receptor / GR / Nuclear receptor subfamily 3 group C member 1


Mass: 29924.867 Da / Num. of mol.: 1 / Mutation: F602S
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: NR3C1, GRL / Production host: Escherichia coli BL21 (bacteria) / References: UniProt: P04150

-
Non-polymers , 3 types, 5 molecules

#4: Chemical ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE


Mass: 507.181 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Comment: ATP, energy-carrying molecule*YM
#5: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Mg
#6: Chemical ChemComp-DEX / DEXAMETHASONE / 9A-FLUORO-16BETA-METHYLPREDNISOLONE


Mass: 392.461 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C22H29FO5 / Comment: medication, antibiotic*YM

-
Details

Has ligand of interestN

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: Complex of the Glucocorticoid Receptor ligand binding domain, Hsp90 alpha dimer, and the co-chaperone p23
Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT
Molecular weightValue: 0.263 MDa / Experimental value: NO
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Escherichia coli BL21 (bacteria)
Buffer solutionpH: 7.5
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: COPPER / Grid mesh size: 400 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationInstrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 283 K

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: 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 holderCryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER
Image recordingAverage exposure time: 5.9 sec. / Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of real images: 5608
EM imaging opticsEnergyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV

-
Processing

EM software
IDNameVersionCategory
2SerialEMimage acquisition
4CTFFIND4.1CTF correction
9RELION3.0.8initial Euler assignment
10RELION3.0.8final Euler assignment
11RELION3.0.8classification
12RELION3.0.83D reconstruction
13Rosettamodel refinement
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 6062152
SymmetryPoint symmetry: C1 (asymmetric)
3D reconstructionResolution: 2.56 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 140217 / Symmetry type: POINT
Atomic model building

3D fitting-ID: 1 / Source name: PDB / Type: experimental model

IDPDB-IDPdb chain-IDAccession codeInitial refinement model-ID
15FWK

5fwk

A5FWK1
25FWK

5fwk

B5FWK1
31M2Z

1m2z

A1M2Z2
41EJF

1ejf

A1EJF3

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more