+Open data
-Basic information
Entry | Database: PDB / ID: 7ras | ||||||||||||||||||
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Title | Structure of TRPV3 in complex with osthole | ||||||||||||||||||
Components | Transient receptor potential cation channel subfamily V member 3 | ||||||||||||||||||
Keywords | MEMBRANE PROTEIN / TRP channel / V3 | ||||||||||||||||||
Function / homology | Function and homology information negative regulation of hair cycle / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / monoatomic cation channel activity / monoatomic ion channel activity / calcium channel activity / lysosome / receptor complex / membrane ...negative regulation of hair cycle / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / monoatomic cation channel activity / monoatomic ion channel activity / calcium channel activity / lysosome / receptor complex / membrane / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.64 Å | ||||||||||||||||||
Authors | Neuberger, A. / Nadezhdin, K.D. / Sobolevsky, A.I. | ||||||||||||||||||
Funding support | United States, Germany, 5items
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Citation | Journal: EMBO Rep / Year: 2021 Title: Structural mechanism of TRPV3 channel inhibition by the plant-derived coumarin osthole. Authors: Arthur Neuberger / Kirill D Nadezhdin / Eleonora Zakharian / Alexander I Sobolevsky / Abstract: TRPV3, a representative of the vanilloid subfamily of TRP channels, is predominantly expressed in skin keratinocytes and has been implicated in cutaneous sensation and associated with numerous skin ...TRPV3, a representative of the vanilloid subfamily of TRP channels, is predominantly expressed in skin keratinocytes and has been implicated in cutaneous sensation and associated with numerous skin pathologies and cancers. TRPV3 is inhibited by the natural coumarin derivative osthole, an active ingredient of Cnidium monnieri, which has been used in traditional Chinese medicine for the treatment of a variety of human diseases. However, the structural basis of channel inhibition by osthole has remained elusive. Here we present cryo-EM structures of TRPV3 in complex with osthole, revealing two types of osthole binding sites in the transmembrane region of TRPV3 that coincide with the binding sites of agonist 2-APB. Osthole binding converts the channel pore into a previously unidentified conformation with a widely open selectivity filter and closed intracellular gate. Our structures provide insight into competitive inhibition of TRPV3 by osthole and can serve as a template for the design of osthole chemistry-inspired drugs targeting TRPV3-associated diseases. | ||||||||||||||||||
History |
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-Structure visualization
Movie |
Movie viewer |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7ras.cif.gz | 437.8 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ras.ent.gz | 360.9 KB | Display | PDB format |
PDBx/mmJSON format | 7ras.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ras_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7ras_full_validation.pdf.gz | 1.4 MB | Display | |
Data in XML | 7ras_validation.xml.gz | 69.1 KB | Display | |
Data in CIF | 7ras_validation.cif.gz | 101.5 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ra/7ras ftp://data.pdbj.org/pub/pdb/validation_reports/ra/7ras | HTTPS FTP |
-Related structure data
Related structure data | 24385MC 7rauC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 92481.547 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Trpv3 / Plasmid: pEG BacMam / Cell line (production host): HEK293 / Production host: Homo sapiens (human) / References: UniProt: Q8K424 #2: Chemical | ChemComp-A0O / 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 |
-Sample preparation
Component | Name: sample 1 / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||||||||||||||||||||
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Molecular weight | Units: MEGADALTONS / Experimental value: NO | ||||||||||||||||||||||||||||||
Source (natural) | Organism: Mus musculus (house mouse) | ||||||||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||||||||||||||||||||
Buffer solution | pH: 8 | ||||||||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 3 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||||||||||||||||||||
Specimen support | Grid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: C-flat-1.2/1.3 | ||||||||||||||||||||||||||||||
Vitrification | Instrument: FEI VITROBOT MARK IV / Cryogen name: ETHANE / Humidity: 100 % / Chamber temperature: 277 K |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: TFS KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: -2500 nm / Nominal defocus min: -1500 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 2.5 sec. / Electron dose: 58 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3991 |
Image scans | Width: 5760 / Height: 4092 |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1102239 | ||||||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.64 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 68101 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL |