+
Open data
-
Basic information
Entry | Database: PDB / ID: 7xer | ||||||
---|---|---|---|---|---|---|---|
Title | Structure of mTRPV2_Q525T | ||||||
![]() | Transient receptor potential cation channel subfamily V member 2 | ||||||
![]() | ![]() | ||||||
Function / homology | ![]() growth cone membrane / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | ||||||
Biological species | ![]() ![]() ![]() | ||||||
Method | ![]() ![]() ![]() | ||||||
![]() | Su, N. | ||||||
Funding support | ![]()
| ||||||
![]() | ![]() Title: Structural mechanisms of TRPV2 modulation by endogenous and exogenous ligands. Authors: Nannan Su / Wenxuan Zhen / Heng Zhang / Lingyi Xu / Yitian Jin / Xiaoying Chen / Cheng Zhao / Qinrui Wang / Xinyan Wang / Shaowei Li / Han Wen / Wei Yang / Jiangtao Guo / Fan Yang / ![]() Abstract: The transient receptor potential vanilloid 2 (TRPV2) ion channel is a polymodal receptor widely involved in many physiological and pathological processes. Despite many TRPV2 modulators being ...The transient receptor potential vanilloid 2 (TRPV2) ion channel is a polymodal receptor widely involved in many physiological and pathological processes. Despite many TRPV2 modulators being identified, whether and how TRPV2 is regulated by endogenous lipids remains elusive. Here, we report an endogenous cholesterol molecule inside the vanilloid binding pocket (VBP) of TRPV2, with a 'head down, tail up' configuration, resolved at 3.2 Å using cryo-EM. Cholesterol binding antagonizes ligand activation of TRPV2, which is removed from VBP by methyl-β-cyclodextrin (MβCD) as resolved at 2.9 Å. We also observed that estradiol (E2) potentiated TRPV2 activation by 2-aminoethoxydiphenyl borate (2-APB), a classic tool compound for TRP channels. Our cryo-EM structures (resolved at 2.8-3.3 Å) further suggest how E2 disturbed cholesterol binding and how 2-APB bound within the VBP with E2 or without both E2 and endogenous cholesterol, respectively. Therefore, our study has established the structural basis for ligand recognition of the inhibitory endogenous cholesterol and excitatory exogenous 2-APB in TRPV2. | ||||||
History |
|
-
Structure visualization
Structure viewer | Molecule: ![]() ![]() |
---|
-
Downloads & links
-
Download
PDBx/mmCIF format | ![]() | 432.6 KB | Display | ![]() |
---|---|---|---|---|
PDB format | ![]() | 360.3 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Arichive directory | ![]() ![]() | HTTPS FTP |
---|
-Related structure data
Related structure data | ![]() 33158MC ![]() 7xemC ![]() 7xeoC ![]() 7xeuC ![]() 7xevC ![]() 7xewC ![]() 7yepC C: citing same article ( M: map data used to model this data |
---|---|
Similar structure data | Similarity search - Function & homology ![]() |
-
Links
-
Assembly
Deposited unit | ![]()
|
---|---|
1 |
|
-
Components
#1: Protein | Mass: 86031.172 Da / Num. of mol.: 4 / Mutation: Q525T Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() ![]() ![]() #2: Chemical | ChemComp-CLR / ![]() Has ligand of interest | Y | |
---|
-Experimental details
-Experiment
Experiment | Method: ![]() |
---|---|
EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: ![]() |
-
Sample preparation
Component | Name: mTRPV2_Q525T / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
---|---|
Source (natural) | Organism: ![]() ![]() ![]() |
Source (recombinant) | Organism: ![]() ![]() |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied![]() ![]() |
Vitrification![]() | Cryogen name: ETHANE |
-
Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
---|---|
Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source![]() ![]() |
Electron lens | Mode: BRIGHT FIELD![]() ![]() |
Image recording | Average exposure time: 8 sec. / Electron dose: 62 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-
Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
CTF correction![]() | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction![]() | Resolution: 2.47 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 208037 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
|