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- PDB-7xj1: Structure of human TRPV3_G573S in complex with Trpvicin in C2 symmetry -
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Open data
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Basic information
Entry | Database: PDB / ID: 7xj1 | ||||||
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Title | Structure of human TRPV3_G573S in complex with Trpvicin in C2 symmetry | ||||||
![]() | Fusion protein of Transient receptor potential cation channel subfamily V member 3 and 3C-GFP | ||||||
![]() | MEMBRANE PROTEIN / channel | ||||||
Function / homology | ![]() osmosensory signaling pathway / calcium ion import across plasma membrane / actin filament organization / calcium channel activity / cilium / plasma membrane Similarity search - Function | ||||||
Biological species | ![]() | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.93 Å | ||||||
![]() | Fan, J. / Yue, Z. / Jiang, D. / Lei, X. | ||||||
Funding support | ![]()
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![]() | ![]() Title: Structural basis of TRPV3 inhibition by an antagonist. Authors: Junping Fan / Linghan Hu / Zongwei Yue / Daohong Liao / Fusheng Guo / Han Ke / Daohua Jiang / Yong Yang / Xiaoguang Lei / ![]() Abstract: The TRPV3 channel plays vital roles in skin physiology. Dysfunction of TRPV3 causes skin diseases, including Olmsted syndrome. However, the lack of potent and selective inhibitors impedes the ...The TRPV3 channel plays vital roles in skin physiology. Dysfunction of TRPV3 causes skin diseases, including Olmsted syndrome. However, the lack of potent and selective inhibitors impedes the validation of TRPV3 as a therapeutic target. In this study, we identified Trpvicin as a potent and subtype-selective inhibitor of TRPV3. Trpvicin exhibits pharmacological potential in the inhibition of itch and hair loss in mouse models. Cryogenic electron microscopy structures of TRPV3 and the pathogenic G573S mutant complexed with Trpvicin reveal detailed ligand-binding sites, suggesting that Trpvicin inhibits the TRPV3 channel by stabilizing it in a closed state. Our G573S mutant structures demonstrate that the mutation causes a dilated pore, generating constitutive opening activity. Trpvicin accesses additional binding sites inside the central cavity of the G573S mutant to remodel the channel symmetry and block the channel. Together, our results provide mechanistic insights into the inhibition of TRPV3 by Trpvicin and support TRPV3-related drug development. | ||||||
History |
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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Download
PDBx/mmCIF format | ![]() | 458.3 KB | Display | ![]() |
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PDB format | ![]() | 349 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
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-Related structure data
Related structure data | ![]() 33216MC ![]() 7xj0C ![]() 7xj2C ![]() 7xj3C 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
#1: Protein | Mass: 120865.406 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Details: The domain (792-799) is PreScission Site. The rest domain (800-1033) is corresponding to this sfGFP (2-235 amino acids).,The domain (792-799) is PreScission Site. The rest domain (800-1033) ...Details: The domain (792-799) is PreScission Site. The rest domain (800-1033) is corresponding to this sfGFP (2-235 amino acids).,The domain (792-799) is PreScission Site. The rest domain (800-1033) is corresponding to this sfGFP (2-235 amino acids). Source: (gene. exp.) ![]() ![]() #2: Chemical | ChemComp-6OU / [( #3: Chemical | ChemComp-EQK / 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: TRPV3 in complex with an antagonist / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 0.36 MDa / Experimental value: NO |
Source (natural) | Organism: ![]() |
Source (recombinant) | Organism: ![]() |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
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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 defocus max: 2500 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 60 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
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Processing
Software | Name: PHENIX / Version: 1.17.1_3660: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 152978 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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