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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Structure of mTRPV2_2-APB | |||||||||
![]() | map of mTRPV2_2-APB | |||||||||
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Function / homology | ![]() growth cone membrane / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / calcium ion import across plasma membrane / positive regulation of axon extension / endomembrane system / monoatomic cation channel activity / axonal growth cone / calcium channel activity ...growth cone membrane / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / calcium ion import across plasma membrane / positive regulation of axon extension / endomembrane system / monoatomic cation channel activity / axonal growth cone / calcium channel activity / melanosome / lamellipodium / positive regulation of cold-induced thermogenesis / cell body / negative regulation of cell population proliferation / axon / cell surface / identical protein binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.27 Å | |||||||||
![]() | Su N | |||||||||
Funding support | ![]()
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![]() | ![]() 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
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 32.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 14.6 KB 14.6 KB | Display Display | ![]() |
Images | ![]() | 55.9 KB | ||
Others | ![]() ![]() | 31.6 MB 31.6 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 800.6 KB | Display | ![]() |
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Full document | ![]() | 800.1 KB | Display | |
Data in XML | ![]() | 10.9 KB | Display | |
Data in CIF | ![]() | 12.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7xevMC ![]() 7xemC ![]() 7xeoC ![]() 7xerC ![]() 7xeuC ![]() 7xewC ![]() 7yepC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
File | ![]() | ||||||||||||||||||||
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Annotation | map of mTRPV2_2-APB | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.014 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: half map of mTRPV2 2-APB
File | emd_33160_half_map_1.map | ||||||||||||
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Annotation | half map of mTRPV2_2-APB | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: half map of mTRPV2 2-APB
File | emd_33160_half_map_2.map | ||||||||||||
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Annotation | half map of mTRPV2_2-APB | ||||||||||||
Projections & Slices |
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Density Histograms |
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Sample components
-Entire : mTRPV2_2-APB
Entire | Name: mTRPV2_2-APB |
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Components |
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-Supramolecule #1: mTRPV2_2-APB
Supramolecule | Name: mTRPV2_2-APB / type: organelle_or_cellular_component / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
-Macromolecule #1: Transient receptor potential cation channel subfamily V member 2
Macromolecule | Name: Transient receptor potential cation channel subfamily V member 2 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 86.058195 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MTSASNPPAF RLETSDGDEE GSAEVNKGKN EPPPMESPFQ GEDRNFSPQI KVNLNYRKGL GPSQQDPNRF DRDRLFSVVS RGVPEELTG LLEYLRRTSK YLTDSAYTEG STGKTCLMKA VLNLQDGVNA CILPLLQIDR DSGNPQPLVN AQCTDEFYRG H SALHIAIE ...String: MTSASNPPAF RLETSDGDEE GSAEVNKGKN EPPPMESPFQ GEDRNFSPQI KVNLNYRKGL GPSQQDPNRF DRDRLFSVVS RGVPEELTG LLEYLRRTSK YLTDSAYTEG STGKTCLMKA VLNLQDGVNA CILPLLQIDR DSGNPQPLVN AQCTDEFYRG H SALHIAIE KRSLWCVKLL VENGANVHIR ACGRFFQKHQ GTCFYFGELP LSLAACTKQW DVVTYLLENP HQPASLEATD SL GNTVLHA LVMIADNSPE NSALVIHMYD SLLQMGARLC PTVQLEDICN HQGLTPLKLA AKEGKIEIFR HILQREFSGL YQP LSRKFT EWCYGPVRVS LYDLSSVDSW EKNSVLEIIA FHCKSPHRHR MVVLEPLNKL LQEKWDRLIP RFFFNFACYL VYMI IFTIV AYHQPSLEQP AIPSSKATFG DSMLLLGHIL ILLGGIYLLL GQLWYFWRRR LFIWISFMDS YFEILFLVQA LLTVL SQVL RFVETEWYLP LLVSSLVLGW LNLLYYTRGF QHTGIYSVMI QKVILRDLLR FLLVYLVFLF GFAVALVSLS REARSP KAP EDSNTTVTEK PTLGQEEEPV PYGGILDASL ELFKFTIGMG ELAFQEQLRF RGVVLLLLLA YVLLTYVLLL NMLIALM SE TVNSVATDSW SIWKLQKAIS VLEMENGYWW CRRKRHRAGR LLKVGTKGDG IPDERWCFRV EEVNWAAWEK TLPTLSED P SGAGITGYKK NPTSKPGKNS ASEEDHLPLQ VLQSH |
-Macromolecule #2: 2-aminoethyl diphenylborinate
Macromolecule | Name: 2-aminoethyl diphenylborinate / type: ligand / ID: 2 / Number of copies: 4 / Formula: FZ4 |
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Molecular weight | Theoretical: 225.094 Da |
Chemical component information | ![]() ChemComp-FZ4: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 2 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K2 SUMMIT (4k x 4k) / Average exposure time: 8.0 sec. / Average electron dose: 62.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.5 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.27 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 68874 |
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Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |