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- EMDB-42996: Inactivated-state cryo-EM structure of human TRPV3 in presence of... -
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Open data
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Basic information
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Title | Inactivated-state cryo-EM structure of human TRPV3 in presence of tetrahydrocannabivarin (THCV) in cNW30 nanodiscs | ||||||||||||||||||
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![]() | transient receptor potential V family member 3 / TRP / channel / TRPV3 / TRP channels / membrane protein / tetrahydrocannabivarin / THCV | ||||||||||||||||||
Function / homology | ![]() negative regulation of hair cycle / TRP channels / response to temperature stimulus / positive regulation of calcium ion import / calcium ion transmembrane transport / calcium channel activity / receptor complex / lysosome / identical protein binding / plasma membrane / cytoplasm Similarity search - Function | ||||||||||||||||||
Biological species | ![]() | ||||||||||||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.63 Å | ||||||||||||||||||
![]() | Nadezhdin KD / Neuberger A / Sobolevsky AI | ||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: TRPV3 activation by different agonists accompanied by lipid dissociation from the vanilloid site. Authors: Kirill D Nadezhdin / Arthur Neuberger / Lena S Khosrof / Irina A Talyzina / Jeffrey Khau / Maria V Yelshanskaya / Alexander I Sobolevsky / ![]() Abstract: TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while ...TRPV3 represents both temperature- and ligand-activated transient receptor potential (TRP) channel. Physiologically relevant opening of TRPV3 channels by heat has been captured structurally, while opening by agonists has only been observed in structures of mutant channels. Here, we present cryo-EM structures that illuminate opening and inactivation of wild-type human TRPV3 in response to binding of two types of agonists: either the natural cannabinoid tetrahydrocannabivarin (THCV) or synthetic agonist 2-aminoethoxydiphenylborane (2-APB). We found that THCV binds to the vanilloid site, while 2-APB binds to the S1-S4 base and ARD-TMD linker sites. Despite binding to distally located sites, both agonists induce similar pore opening and cause dissociation of a lipid that occupies the vanilloid site in their absence. Our results uncover different but converging allosteric pathways through which small-molecule agonists activate TRPV3 and provide a framework for drug design and understanding the role of lipids in ion channel function. | ||||||||||||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.6 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.3 KB 19.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 8.5 KB | Display | ![]() |
Images | ![]() | 91.5 KB | ||
Filedesc metadata | ![]() | 6.9 KB | ||
Others | ![]() ![]() | 59.2 MB 59.2 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8v6mMC ![]() 8v6kC ![]() 8v6lC ![]() 8v6nC ![]() 8v6oC 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: 0.83 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_42996_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_42996_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
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Sample components
-Entire : full-length human TRPV3 in complex with THCV
Entire | Name: full-length human TRPV3 in complex with THCV |
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Components |
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-Supramolecule #1: full-length human TRPV3 in complex with THCV
Supramolecule | Name: full-length human TRPV3 in complex with THCV / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 370 KDa |
-Macromolecule #1: Transient receptor potential cation channel subfamily V member 3
Macromolecule | Name: Transient receptor potential cation channel subfamily V member 3 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 92.680016 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MKAHPKEMVP LMGKRVAAPS GNPAILPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS PPVFSKPMDS NIRQCISGNC DDMDSPQSP QDDVTETPSN PNSPSAQLAK EEQRRKKRRL KKRIFAAVSE GCVEELVELL VELQELCRRR HDEDVPDFLM H KLTASDTG ...String: MKAHPKEMVP LMGKRVAAPS GNPAILPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS PPVFSKPMDS NIRQCISGNC DDMDSPQSP QDDVTETPSN PNSPSAQLAK EEQRRKKRRL KKRIFAAVSE GCVEELVELL VELQELCRRR HDEDVPDFLM H KLTASDTG KTCLMKALLN INPNTKEIVR ILLAFAEEND ILGRFINAEY TEEAYEGQTA LNIAIERRQG DIAALLIAAG AD VNAHAKG AFFNPKYQHE GFYFGETPLA LAACTNQPEI VQLLMEHEQT DITSRDSRGN NILHALVTVA EDFKTQNDFV KRM YDMILL RSGNWELETT RNNDGLTPLQ LAAKMGKAEI LKYILSREIK EKRLRSLSRK FTDWAYGPVS SSLYDLTNVD TTTD NSVLE ITVYNTNIDN RHEMLTLEPL HTLLHMKWKK FAKHMFFLSF CFYFFYNITL TLVSYYRPRE EEAIPHPLAL THKMG WLQL LGRMFVLIWA MCISVKEGIA IFLLRPSDLQ SILSDAWFHF VFFIQAVLVI LSVFLYLFAY KEYLACLVLA MALGWA NML YYTRGFQSMG MYSVMIQKVI LHDVLKFLFV YIVFLLGFGV ALASLIEKCP KDNKDCSSYG SFSDAVLELF KLTIGLG DL NIQQNSKYPI LFLFLLITYV ILTFVLLLNM LIALMGETVE NVSKESERIW RLQRARTILE FEKMLPEWLR SRFRMGEL C KVAEDDFRLC LRINEVKWTE WKTHVSFLNE DPGPVRRTAD FNKIQDSSRN NSKTTLNAFE EVEEFPETSV LVPRGSAAA WSHPQFEK UniProtKB: Transient receptor potential cation channel subfamily V member 3 |
-Macromolecule #2: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...
Macromolecule | Name: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate type: ligand / ID: 2 / Number of copies: 12 / Formula: POV |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-POV: |
-Macromolecule #3: Tetrahydrocannabivarin
Macromolecule | Name: Tetrahydrocannabivarin / type: ligand / ID: 3 / Number of copies: 4 / Formula: I8E |
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Molecular weight | Theoretical: 286.409 Da |
Chemical component information | ![]() ChemComp-I8E: |
-Macromolecule #4: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 4 / Number of copies: 3 |
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Molecular weight | Theoretical: 22.99 Da |
-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: 8 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Support film - Material: GOLD / Support film - topology: HOLEY | |||||||||||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 100 % / Chamber temperature: 295 K / Instrument: FEI VITROBOT MARK IV | |||||||||||||||
Details | human TRPV3 in cNW30 nanodiscs |
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Electron microscopy
Microscope | TFS KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 1 / Number real images: 9938 / Average exposure time: 3.4 sec. / Average electron dose: 60.0 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: 1.75 µm / Nominal defocus min: 0.5 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Refinement | Space: REAL |
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Output model | ![]() PDB-8v6m: |