+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-33774 | |||||||||
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Title | 2-APB bound state of mTRPV2 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | mTRPV2 / 2-APB / STRUCTURAL PROTEIN / MEMBRANE PROTEIN | |||||||||
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 / axonal growth cone / monoatomic cation channel activity / calcium channel activity / melanosome ...growth cone membrane / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / endomembrane system / positive regulation of axon extension / axonal growth cone / monoatomic cation channel activity / 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 | Mus musculus (house mouse) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 2.83 Å | |||||||||
Authors | Su N | |||||||||
Funding support | China, 1 items
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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
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_33774.map.gz | 49.3 MB | EMDB map data format | |
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Header (meta data) | emd-33774-v30.xml emd-33774.xml | 14.6 KB 14.6 KB | Display Display | EMDB header |
Images | emd_33774.png | 70.7 KB | ||
Masks | emd_33774_msk_1.map | 52.7 MB | Mask map | |
Filedesc metadata | emd-33774.cif.gz | 5.6 KB | ||
Others | emd_33774_half_map_1.map.gz emd_33774_half_map_2.map.gz | 14 MB 14 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-33774 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-33774 | HTTPS FTP |
-Validation report
Summary document | emd_33774_validation.pdf.gz | 831.7 KB | Display | EMDB validaton report |
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Full document | emd_33774_full_validation.pdf.gz | 831.3 KB | Display | |
Data in XML | emd_33774_validation.xml.gz | 11.8 KB | Display | |
Data in CIF | emd_33774_validation.cif.gz | 13.7 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33774 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-33774 | HTTPS FTP |
-Related structure data
Related structure data | 7yepMC 7xemC 7xeoC 7xerC 7xeuC 7xevC 7xewC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_33774.map.gz / Format: CCP4 / Size: 52.7 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.93 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Mask #1
File | emd_33774_msk_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #2
File | emd_33774_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_33774_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : complex of mTRPV2 and 2-APB
Entire | Name: complex of mTRPV2 and 2-APB |
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Components |
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-Supramolecule #1: complex of mTRPV2 and 2-APB
Supramolecule | Name: complex of mTRPV2 and 2-APB / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Mus musculus (house mouse) |
-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: Mus musculus (house mouse) |
Molecular weight | Theoretical: 86.058195 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 UniProtKB: Transient receptor potential cation channel subfamily V member 2 |
-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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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 5 mg/mL |
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Buffer | pH: 7.4 |
Vitrification | Cryogen name: ETHANE |
-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: 6.0 sec. / Average electron dose: 52.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
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 |
-Image processing
Startup model | Type of model: OTHER |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 2.83 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 121357 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |