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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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Function / homology | ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||||||||
Biological species | ![]() ![]() | |||||||||||||||
Method | ![]() ![]() ![]() | |||||||||||||||
![]() | 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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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
Arichive directory | ![]() ![]() | HTTPS FTP |
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-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: ![]() |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
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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![]() ![]() | |||||||||||||||||||||||||||||||||||
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![]() ![]() |
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![]() | ||||||||||||||||||||||||||||||||||||||||
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 | ||||||||||||||||||||||||||||||||||||||||
Refine LS restraints |
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