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- PDB-8qmo: Cryo-EM structure of the benzo[a]pyrene-bound Hsp90-XAP2-AHR complex -
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Open data
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Basic information
Entry | Database: PDB / ID: 8qmo | |||||||||||||||
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Title | Cryo-EM structure of the benzo[a]pyrene-bound Hsp90-XAP2-AHR complex | |||||||||||||||
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![]() | TRANSCRIPTION / detoxification / chemical pollutants / exposome | |||||||||||||||
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 / TFIID-class transcription factor complex binding / aryl hydrocarbon receptor 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 / ESR-mediated signaling / cAMP-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 / placenta development / tau protein binding / PPARA activates gene expression / response to toxic substance / Regulation of actin dynamics for phagocytic cup formation / transcription coactivator binding / kinase binding / histone deacetylase binding / negative regulation of inflammatory response / 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: 2.76 Å | |||||||||||||||
![]() | Kwong, H.S. / Grandvuillemin, L. / Sirounian, S. / Ancelin, A. / Lai-Kee-Him, J. / Carivenc, C. / Lancey, C. / Ragan, T.J. / Hesketh, E.L. / Bourguet, W. / Gruszczyk, J. | |||||||||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural Insights into the Activation of Human Aryl Hydrocarbon Receptor by the Environmental Contaminant Benzo[a]pyrene and Structurally Related Compounds. Authors: Hok-Sau Kwong / Matteo Paloni / Loïc Grandvuillemin / Savannah Sirounian / Aurélie Ancelin / Josephine Lai-Kee-Him / Marina Grimaldi / Coralie Carivenc / Claudia Lancey / Timothy J Ragan / ...Authors: Hok-Sau Kwong / Matteo Paloni / Loïc Grandvuillemin / Savannah Sirounian / Aurélie Ancelin / Josephine Lai-Kee-Him / Marina Grimaldi / Coralie Carivenc / Claudia Lancey / Timothy J Ragan / Emma L Hesketh / Patrick Balaguer / Alessandro Barducci / Jakub Gruszczyk / William Bourguet / ![]() ![]() Abstract: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor belonging to the bHLH/PAS protein family and responding to hundreds of natural and chemical substances. It is primarily ...The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor belonging to the bHLH/PAS protein family and responding to hundreds of natural and chemical substances. It is primarily involved in the defense against chemical insults and bacterial infections or in the adaptive immune response, but also in the development of pathological conditions ranging from inflammatory to neoplastic disorders. Despite its prominent roles in many (patho)physiological processes, the lack of high-resolution structural data has precluded for thirty years an in-depth understanding of the structural mechanisms underlying ligand-binding specificity, promiscuity and activation of AHR. We recently reported a cryogenic electron microscopy (cryo-EM) structure of human AHR bound to the natural ligand indirubin, the chaperone Hsp90 and the co-chaperone XAP2 that provided the first experimental visualization of its ligand-binding PAS-B domain. Here, we report a 2.75 Å resolution structure of the AHR complex bound to the environmental pollutant benzo[a]pyrene (B[a]P). The structure substantiates the existence of a bipartite PAS-B ligand-binding pocket with a geometrically constrained primary binding site controlling ligand binding specificity and affinity, and a secondary binding site contributing to the binding promiscuity of AHR. We also report a docking study of B[a]P congeners that validates the B[a]P-bound PAS-B structure as a suitable model for accurate computational ligand binding assessment. Finally, comparison of our agonist-bound complex with the recently reported structures of mouse and fruit fly AHR PAS-B in different activation states suggests a ligand-induced loop conformational change potentially involved in the regulation of AHR function. | |||||||||||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 646.9 KB | Display | ![]() |
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PDB format | ![]() | 533.3 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 | ![]() | 60.6 KB | Display | |
Data in CIF | ![]() | 90.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 18498MC 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: 49492.559 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/MOO.gif)
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#4: Chemical | #5: Chemical | #6: Chemical | #7: Chemical | ChemComp-W62 / | |
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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: Benzo[a]pyrene-bound Hsp90-XAP2-AHR complex / Type: COMPLEX / Entity ID: #1-#3 / Source: RECOMBINANT | |||||||||||||||||||||||||||||||||||
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Molecular weight | Value: 0.254 MDa / Experimental value: NO | |||||||||||||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() ![]() | |||||||||||||||||||||||||||||||||||
Buffer solution | pH: 7 | |||||||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 0.18 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: 298 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: 2300 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 2 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: 9849 |
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Processing
EM software |
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CTF correction | Type: PHASE FLIPPING ONLY | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 6327916 | ||||||||||||||||||||||||||||||||||||||||
Symmetry | Point symmetry: C1 (asymmetric) | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 2.76 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 630113 / Num. of class averages: 1 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7ZUB Accession code: 7ZUB / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||||||||||
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