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- PDB-8v6l: Open-state cryo-EM structure of human TRPV3 in presence of tetrah... -
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Open data
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Basic information
Entry | Database: PDB / ID: 8v6l | ||||||||||||||||||
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Title | Open-state cryo-EM structure of human TRPV3 in presence of tetrahydrocannabivarin (THCV) in cNW30 nanodiscs | ||||||||||||||||||
![]() | Transient receptor potential cation channel subfamily V member 3 | ||||||||||||||||||
![]() | MEMBRANE PROTEIN / transient receptor potential V family member 3 / TRP / channel / TRPV3 / TRP channels / tetrahydrocannabivarin / THCV | ||||||||||||||||||
Function / homology | ![]() negative regulation of hair cycle / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / calcium ion transmembrane transport / calcium channel activity / receptor complex / lysosome / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.68 Å | ||||||||||||||||||
![]() | Nadezhdin, K.D. / Neuberger, A. / Sobolevsky, A.I. | ||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site. Authors: Kirill D Nadezhdin / Arthur Neuberger / Lena S Khosrof / Irina A Talyzina / Jeffrey Khau / Maria V Yelshanskaya / Alexander I Sobolevsky / ![]() Abstract: TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while ...TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while opening by agonists has only been observed in structures of mutant channels. Here, we present cryo-EM structures that illuminate opening and inactivation of wild-type human TRPV3 in response to binding of two types of agonists: either the natural cannabinoid tetrahydrocannabivarin (THCV) or synthetic agonist 2-aminoethoxydiphenylborane (2-APB). We found that THCV binds to the vanilloid site, while 2-APB binds to the S1-S4 base and ARD-TMD linker sites. Despite binding to distally located sites, both agonists induce similar pore opening and cause dissociation of a lipid that occupies the vanilloid site in their absence. Our results uncover different but converging allosteric pathways through which small-molecule agonists activate TRPV3 and provide a framework for drug design and understanding the role of lipids in ion channel 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 | ![]() | 490.3 KB | Display | ![]() |
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PDB format | ![]() | 407.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 42995MC ![]() 8v6kC ![]() 8v6mC ![]() 8v6nC ![]() 8v6oC C: citing same article ( M: map data used to model this data |
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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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1 |
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Components
#1: Protein | Mass: 92680.016 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() #2: Chemical | ChemComp-POV / ( #3: Chemical | ChemComp-I8E / #4: Chemical | 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: full-length human TRPV3 in complex with THCV / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | |||||||||||||||||||||||||
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Molecular weight | Value: 0.37 MDa / Experimental value: NO | |||||||||||||||||||||||||
Source (natural) | Organism: ![]() | |||||||||||||||||||||||||
Source (recombinant) | Organism: ![]() | |||||||||||||||||||||||||
Buffer solution | pH: 8 | |||||||||||||||||||||||||
Buffer component |
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Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: human TRPV3 in cNW30 nanodiscs | |||||||||||||||||||||||||
Specimen support | Grid type: UltrAuFoil R1.2/1.3 | |||||||||||||||||||||||||
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: TFS KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1750 nm / Nominal defocus min: 500 nm / Cs: 2.7 mm |
Image recording | Average exposure time: 3.4 sec. / Electron dose: 60 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 9938 |
Image scans | Width: 5760 / Height: 4092 |
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Processing
EM software | Name: PHENIX / Version: 1.18 / Category: model refinement | ||||||||||||||||||||||||
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CTF correction | Type: NONE | ||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2951936 | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.68 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 36121 / Symmetry type: POINT | ||||||||||||||||||||||||
Atomic model building | Space: REAL | ||||||||||||||||||||||||
Refine LS restraints |
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