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Open data
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Basic information
Entry | Database: PDB / ID: 7zub | ||||||||||||
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Title | Cryo-EM structure of the indirubin-bound Hsp90-XAP2-AHR complex | ||||||||||||
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![]() | GENE REGULATION / complex / nuclear receptor / chemical pollutants / detoxification / cancer | ||||||||||||
Function / homology | ![]() GAF domain binding / negative regulation of T cell mediated immune response to tumor cell / cytosolic aryl hydrocarbon receptor complex / regulation of B cell proliferation / cellular response to molecule of bacterial origin / regulation of adaptive immune response / : / cellular response to 2,3,7,8-tetrachlorodibenzodioxine / nuclear aryl hydrocarbon receptor complex / HSP90-CDC37 chaperone complex ...GAF domain binding / negative regulation of T cell mediated immune response to tumor cell / cytosolic aryl hydrocarbon receptor complex / regulation of B cell proliferation / cellular response to molecule of bacterial origin / regulation of adaptive immune response / : / cellular response to 2,3,7,8-tetrachlorodibenzodioxine / nuclear aryl hydrocarbon receptor complex / HSP90-CDC37 chaperone complex / positive regulation of cyclin-dependent protein kinase activity / negative regulation of proteasomal protein catabolic process / Aryl hydrocarbon receptor signalling / aryl hydrocarbon receptor complex / dynein axonemal particle / histone methyltransferase binding / regulation of protein kinase A signaling / Xenobiotics / protein targeting to mitochondrion / positive regulation of protein localization to cell surface / ATP-dependent protein binding / protein kinase regulator activity / Phase I - Functionalization of compounds / protein maturation by protein folding / negative regulation of protein metabolic process / positive regulation of tau-protein kinase activity / telomerase holoenzyme complex assembly / Respiratory syncytial virus genome replication / Uptake and function of diphtheria toxin / TPR domain binding / blood vessel development / positive regulation of transforming growth factor beta receptor signaling pathway / Assembly and release of respiratory syncytial virus (RSV) virions / E-box binding / dendritic growth cone / positive regulation of phosphoprotein phosphatase activity / aryl hydrocarbon receptor binding / TFIID-class transcription factor complex binding / Sema3A PAK dependent Axon repulsion / The NLRP3 inflammasome / regulation of protein ubiquitination / HSF1-dependent transactivation / response to unfolded protein / negative regulation of proteasomal ubiquitin-dependent protein catabolic process / telomere maintenance via telomerase / chaperone-mediated protein complex assembly / HSF1 activation / Attenuation phase / cellular response to interleukin-4 / Endogenous sterols / RHOBTB2 GTPase cycle / cis-regulatory region sequence-specific DNA binding / Purinergic signaling in leishmaniasis infection / axonal growth cone / DNA polymerase binding / supramolecular fiber organization / cellular response to cAMP / cellular response to forskolin / : / heat shock protein binding / HSP90 chaperone cycle for steroid hormone receptors (SHR) in the presence of ligand / TBP-class protein binding / nitric-oxide synthase regulator activity / Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation / xenobiotic metabolic process / cAMP-mediated signaling / ESR-mediated signaling / peptidyl-prolyl cis-trans isomerase activity / positive regulation of cell differentiation / ATP-dependent protein folding chaperone / peptide binding / circadian regulation of gene expression / Hsp90 protein binding / DDX58/IFIH1-mediated induction of interferon-alpha/beta / tau protein binding / placenta development / PPARA activates gene expression / response to toxic substance / Regulation of actin dynamics for phagocytic cup formation / kinase binding / transcription coactivator binding / negative regulation of inflammatory response / histone deacetylase binding / Chaperone Mediated Autophagy / The role of GTSE1 in G2/M progression after G2 checkpoint / nuclear receptor activity / regulation of protein localization / positive regulation of nitric oxide biosynthetic process / sequence-specific double-stranded DNA binding / double-stranded RNA binding / disordered domain specific binding / unfolded protein binding / melanosome / protein folding / MHC class II protein complex binding / cellular response to heat / regulation of gene expression / secretory granule lumen / Estrogen-dependent gene expression / RNA polymerase II-specific DNA-binding transcription factor binding Similarity search - Function | ||||||||||||
Biological species | ![]() | ||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.85 Å | ||||||||||||
![]() | Gruszczyk, J. / Savva, C.G. / Lai-Kee-Him, J. / Bous, J. / Ancelin, A. / Kwong, H.S. / Grandvuillemin, L. / Bourguet, W. | ||||||||||||
Funding support | European Union, ![]()
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![]() | ![]() Title: Cryo-EM structure of the agonist-bound Hsp90-XAP2-AHR cytosolic complex. Authors: Jakub Gruszczyk / Loïc Grandvuillemin / Josephine Lai-Kee-Him / Matteo Paloni / Christos G Savva / Pierre Germain / Marina Grimaldi / Abdelhay Boulahtouf / Hok-Sau Kwong / Julien Bous / ...Authors: Jakub Gruszczyk / Loïc Grandvuillemin / Josephine Lai-Kee-Him / Matteo Paloni / Christos G Savva / Pierre Germain / Marina Grimaldi / Abdelhay Boulahtouf / Hok-Sau Kwong / Julien Bous / Aurélie Ancelin / Cherine Bechara / Alessandro Barducci / Patrick Balaguer / William Bourguet / ![]() ![]() ![]() Abstract: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including ...The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates a broad spectrum of (patho)physiological processes in response to numerous substances including pollutants, natural products and metabolites. However, the scarcity of structural data precludes understanding of how AHR is activated by such diverse compounds. Our 2.85 Å structure of the human indirubin-bound AHR complex with the chaperone Hsp90 and the co-chaperone XAP2, reported herein, reveals a closed conformation Hsp90 dimer with AHR threaded through its lumen and XAP2 serving as a brace. Importantly, we disclose the long-awaited structure of the AHR PAS-B domain revealing a unique organisation of the ligand-binding pocket and the structural determinants of ligand-binding specificity and promiscuity of the receptor. By providing structural details of the molecular initiating event leading to AHR activation, our study rationalises almost forty years of biochemical data and provides a framework for future mechanistic studies and structure-guided drug design. | ||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 674 KB | Display | ![]() |
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PDB format | ![]() | 555.2 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.3 MB | Display | ![]() |
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Full document | ![]() | 1.3 MB | Display | |
Data in XML | ![]() | 59.1 KB | Display | |
Data in CIF | ![]() | 89.8 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 14971MC 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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Components
-Protein , 3 types, 4 molecules ABCD
#1: Protein | Mass: 84213.141 Da / Num. of mol.: 2 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Protein | | Mass: 37691.047 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #3: Protein | | Mass: 49767.879 Da / Num. of mol.: 1 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() |
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-Non-polymers , 4 types, 7 molecules ![](data/chem/img/ADP.gif)
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![](data/chem/img/JY6.gif)
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#4: Chemical | #5: Chemical | #6: Chemical | #7: Chemical | ChemComp-JY6 / ( | |
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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: Hsp90-XAP2-AHR complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT | |||||||||||||||||||||||||||||||||||
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Molecular weight | Value: 0.256 MDa / Experimental value: YES | |||||||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7 | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | |||||||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 300 divisions/in. / Grid type: C-flat-1.2/1.3 | |||||||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 295 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: 81000 X / Nominal defocus max: 1500 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 50 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 3 sec. / Electron dose: 1.1 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9300 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
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Processing
Software | Name: PHENIX / Version: 1.20_4459: / Classification: refinement | ||||||||||||||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 11546649 | ||||||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.85 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 678724 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building |
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