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- EMDB-25650: Activated state of 2-APB and CBD-bound wildtype rat TRPV2 in nanodiscs -
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Open data
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Basic information
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Title | Activated state of 2-APB and CBD-bound wildtype rat TRPV2 in nanodiscs | |||||||||
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![]() | TRP channel / ion channel / TRPV / TRANSPORT PROTEIN | |||||||||
Function / homology | ![]() 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 / melanosome ...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 / 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: 3.7 Å | |||||||||
![]() | Pumroy RA / Protopopova AD | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Structural insights into TRPV2 activation by small molecules. Authors: Ruth A Pumroy / Anna D Protopopova / Tabea C Fricke / Iris U Lange / Ferdinand M Haug / Phuong T Nguyen / Pamela N Gallo / Bárbara B Sousa / Gonçalo J L Bernardes / Vladimir Yarov-Yarovoy ...Authors: Ruth A Pumroy / Anna D Protopopova / Tabea C Fricke / Iris U Lange / Ferdinand M Haug / Phuong T Nguyen / Pamela N Gallo / Bárbara B Sousa / Gonçalo J L Bernardes / Vladimir Yarov-Yarovoy / Andreas Leffler / Vera Y Moiseenkova-Bell / ![]() ![]() ![]() ![]() Abstract: Transient receptor potential vanilloid 2 (TRPV2) is involved in many critical physiological and pathophysiological processes, making it a promising drug target. Here we present cryo-electron ...Transient receptor potential vanilloid 2 (TRPV2) is involved in many critical physiological and pathophysiological processes, making it a promising drug target. Here we present cryo-electron microscopy (cryo-EM) structures of rat TRPV2 in lipid nanodiscs activated by 2-aminoethoxydiphenyl borate (2-APB) and propose a TRPV2-specific 2-ABP binding site at the interface of S5 of one monomer and the S4-S5 linker of the adjacent monomer. In silico docking and electrophysiological studies confirm the key role of His521 and Arg539 in 2-APB activation of TRPV2. Additionally, electrophysiological experiments show that the combination of 2-APB and cannabidiol has a synergetic effect on TRPV2 activation, and cryo-EM structures demonstrate that both drugs were able to bind simultaneously. Together, our cryo-EM structures represent multiple functional states of the channel, providing a native picture of TRPV2 activation by small molecules and a structural framework for the development of TRPV2-specific activators. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.2 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.1 KB 11.1 KB | Display Display | ![]() |
Images | ![]() | 124.3 KB | ||
Filedesc metadata | ![]() | 5.7 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7t37MC ![]() 7n0mC ![]() 7n0nC ![]() 7t38C C: citing same article ( M: atomic model generated by this map |
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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
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Voxel size | X=Y=Z: 1.07 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Tetramer of wildtype rat TRPV2
Entire | Name: Tetramer of wildtype rat TRPV2 |
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Components |
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-Supramolecule #1: Tetramer of wildtype rat TRPV2
Supramolecule | Name: Tetramer of wildtype rat TRPV2 / type: complex / 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: 86.798891 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MTSASSPPAF RLETSDGDEE GNAEVNKGKQ EPPPMESPFQ REDRNSSPQI KVNLNFIKRP PKNTSAPSQQ EPDRFDRDRL FSVVSRGVP EELTGLLEYL RWNSKYLTDS AYTEGSTGKT CLMKAVLNLQ DGVNACIMPL LQIDKDSGNP KLLVNAQCTD E FYQGHSAL ...String: MTSASSPPAF RLETSDGDEE GNAEVNKGKQ EPPPMESPFQ REDRNSSPQI KVNLNFIKRP PKNTSAPSQQ EPDRFDRDRL FSVVSRGVP EELTGLLEYL RWNSKYLTDS AYTEGSTGKT CLMKAVLNLQ DGVNACIMPL LQIDKDSGNP KLLVNAQCTD E FYQGHSAL HIAIEKRSLQ CVKLLVENGA DVHLRACGRF FQKHQGTCFY FGELPLSLAA CTKQWDVVTY LLENPHQPAS LE ATDSLGN TVLHALVMIA DNSPENSALV IHMYDGLLQM GARLCPTVQL EEISNHQGLT PLKLAAKEGK IEIFRHILQR EFS GPYQPL SRKFTEWCYG PVRVSLYDLS SVDSWEKNSV LEIIAFHCKS PNRHRMVVLE PLNKLLQEKW DRLVSRFFFN FACY LVYMF IFTVVAYHQP SLDQPAIPSS KATFGESMLL LGHILILLGG IYLLLGQLWY FWRRRLFIWI SFMDSYFEIL FLLQA LLTV LSQVLRFMET EWYLPLLVLS LVLGWLNLLY YTRGFQHTGI YSVMIQKVIL RDLLRFLLVY LVFLFGFAVA LVSLSR EAR SPKAPEDNNS TVTEQPTVGQ EEEPAPYRSI LDASLELFKF TIGMGELAFQ EQLRFRGVVL LLLLAYVLLT YVLLLNM LI ALMSETVNHV ADNSWSIWKL QKAISVLEME NGYWWCRRKK HREGRLLKVG TRGDGTPDER WCFRVEEVNW AAWEKTLP T LSEDPSGPGI TGNKKNPTSK PGKNSASEED HLPLQVLQSP UniProtKB: Transient receptor potential cation channel subfamily V member 2 |
-Macromolecule #2: cannabidiol
Macromolecule | Name: cannabidiol / type: ligand / ID: 2 / Number of copies: 4 / Formula: P0T |
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Molecular weight | Theoretical: 314.462 Da |
Chemical component information | ![]() ChemComp-P0T: |
-Macromolecule #3: 2-aminoethyl diphenylborinate
Macromolecule | Name: 2-aminoethyl diphenylborinate / type: ligand / ID: 3 / 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
Buffer | pH: 8 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 42.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.5 µm / Nominal defocus min: 0.5 µm |
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Image processing
Startup model | Type of model: INSILICO MODEL |
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Final reconstruction | Resolution.type: BY AUTHOR / Resolution: 3.7 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 30563 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |