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Yorodumi- PDB-7ugg: Cryo-EM structure of TRPV3 in complex with the anesthetic dyclonine -
+Open data
-Basic information
Entry | Database: PDB / ID: 7ugg | ||||||||||||||||||
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Title | Cryo-EM structure of TRPV3 in complex with the anesthetic dyclonine | ||||||||||||||||||
Components | Transient receptor potential cation channel subfamily V member 3 | ||||||||||||||||||
Keywords | MEMBRANE PROTEIN / Transient Receptor Potential V Family Member 3 / TRP / channel / closed / TRPV3 / anesthetic / dyclonine | ||||||||||||||||||
Function / homology | Function and homology information negative regulation of hair cycle / TRP channels / osmosensory signaling pathway / response to temperature stimulus / positive regulation of calcium ion import / calcium ion import across plasma membrane / monoatomic cation channel activity / actin filament organization / calcium channel activity / cilium ...negative regulation of hair cycle / TRP channels / osmosensory signaling pathway / response to temperature stimulus / positive regulation of calcium ion import / calcium ion import across plasma membrane / monoatomic cation channel activity / actin filament organization / calcium channel activity / cilium / monoatomic ion channel activity / receptor complex / membrane / plasma membrane Similarity search - Function | ||||||||||||||||||
Biological species | Mus musculus (house mouse) | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.16 Å | ||||||||||||||||||
Authors | Neuberger, A. / Nadezhdin, K.D. / Sobolevsky, A.I. | ||||||||||||||||||
Funding support | United States, Germany, 5items
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Citation | Journal: Nat Commun / Year: 2022 Title: Structural mechanism of TRPV3 channel inhibition by the anesthetic dyclonine. Authors: Arthur Neuberger / Kirill D Nadezhdin / Alexander I Sobolevsky / Abstract: Skin diseases are common human illnesses that occur in all cultures, at all ages, and affect between 30% and 70% of individuals globally. TRPV3 is a cation-permeable TRP channel predominantly ...Skin diseases are common human illnesses that occur in all cultures, at all ages, and affect between 30% and 70% of individuals globally. TRPV3 is a cation-permeable TRP channel predominantly expressed in skin keratinocytes, implicated in cutaneous sensation and associated with numerous skin diseases. TRPV3 is inhibited by the local anesthetic dyclonine, traditionally used for topical applications to relieve pain and itch. However, the structural basis of TRPV3 inhibition by dyclonine has remained elusive. Here we present a cryo-EM structure of a TRPV3-dyclonine complex that reveals binding of the inhibitor in the portals which connect the membrane environment surrounding the channel to the central cavity of the channel pore. We propose a mechanism of TRPV3 inhibition in which dyclonine molecules stick out into the channel pore, creating a barrier for ion conductance. The allosteric binding site of dyclonine can serve as a template for the design of new TRPV3-targeting drugs. | ||||||||||||||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7ugg.cif.gz | 477.1 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7ugg.ent.gz | 397.9 KB | Display | PDB format |
PDBx/mmJSON format | 7ugg.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7ugg_validation.pdf.gz | 1.8 MB | Display | wwPDB validaton report |
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Full document | 7ugg_full_validation.pdf.gz | 1.9 MB | Display | |
Data in XML | 7ugg_validation.xml.gz | 91.5 KB | Display | |
Data in CIF | 7ugg_validation.cif.gz | 124.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/ug/7ugg ftp://data.pdbj.org/pub/pdb/validation_reports/ug/7ugg | HTTPS FTP |
-Related structure data
Related structure data | 26488MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 92573.641 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Trpv3 / Production host: Homo sapiens (human) / References: UniProt: Q8K424 #2: Chemical | ChemComp-POV / ( #3: Chemical | ChemComp-N8R / #4: Chemical | #5: Water | ChemComp-HOH / | 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 | Value: 0.09247 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: Mus musculus (house mouse) | |||||||||||||||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) / Cell: Human embryonic kidney 293 / Plasmid: pEG BacMam | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2.2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES Details: mouse TRPV3 in circularized NW30 nanodiscs (cNW30) with soybean lipids | |||||||||||||||||||||||||
Specimen support | Grid material: GOLD / 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: 2000 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 2.5 sec. / Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 6856 |
Image scans | Width: 5760 / Height: 4092 |
-Processing
EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 4413740 | ||||||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.16 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 87876 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7MIJ Accession code: 7MIJ / Source name: PDB / Type: experimental model |