+Open data
-Basic information
Entry | Database: PDB / ID: 7xev | ||||||
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Title | Structure of mTRPV2_2-APB | ||||||
Components | Transient receptor potential cation channel subfamily V member 2 | ||||||
Keywords | STRUCTURAL PROTEIN / mTRPV2 | ||||||
Function / homology | Function and homology information growth cone membrane / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / endomembrane system / positive regulation of axon extension / monoatomic cation channel activity / axonal growth cone / calcium channel activity / positive regulation of cold-induced thermogenesis ...growth cone membrane / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / endomembrane system / positive regulation of axon extension / monoatomic cation channel activity / axonal growth cone / calcium channel activity / positive regulation of cold-induced thermogenesis / melanosome / lamellipodium / cell body / negative regulation of cell population proliferation / axon / cell surface / identical protein binding / plasma membrane Similarity search - Function | ||||||
Biological species | Mus musculus (house mouse) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.27 Å | ||||||
Authors | Su, N. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Chem Biol / Year: 2023 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 |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xev.cif.gz | 821.7 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xev.ent.gz | 691.5 KB | Display | PDB format |
PDBx/mmJSON format | 7xev.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xev_validation.pdf.gz | 1.5 MB | Display | wwPDB validaton report |
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Full document | 7xev_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 7xev_validation.xml.gz | 72.2 KB | Display | |
Data in CIF | 7xev_validation.cif.gz | 106.7 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xe/7xev ftp://data.pdbj.org/pub/pdb/validation_reports/xe/7xev | HTTPS FTP |
-Related structure data
Related structure data | 33160MC 7xemC 7xeoC 7xerC 7xeuC 7xewC 7yepC C: citing same article (ref.) M: map data used to model this data |
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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: 86058.195 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Mus musculus (house mouse) / Gene: Trpv2, Grc / Cell (production host): HEK 293 / Production host: Homo sapiens (human) / References: UniProt: Q9WTR1 #2: Chemical | ChemComp-FZ4 / 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: mTRPV2_2-APB / Type: ORGANELLE OR CELLULAR COMPONENT / Entity ID: #1 / Source: RECOMBINANT |
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Source (natural) | Organism: Mus musculus (house mouse) |
Source (recombinant) | Organism: Homo sapiens (human) / Cell: HEK 293 |
Buffer solution | pH: 7.4 |
Specimen | Conc.: 2 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 1500 nm / Nominal defocus min: 1000 nm / Cs: 2.7 mm |
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 | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.27 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 68874 / Symmetry type: POINT | ||||||||||||||||||||||||
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