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- EMDB-23478: Cryo-EM structure of full-length TRPV1 with capsaicin at 48 degre... -
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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-23478 | |||||||||
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Title | Cryo-EM structure of full-length TRPV1 with capsaicin at 48 degrees Celsius, in an intermediate state, class 2 | |||||||||
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![]() | Heat sensing ion channel / MEMBRANE PROTEIN | |||||||||
Function / homology | ![]() negative regulation of establishment of blood-brain barrier / response to capsazepine / sensory perception of mechanical stimulus / peptide secretion / cellular response to temperature stimulus / excitatory extracellular ligand-gated monoatomic ion channel activity / temperature-gated ion channel activity / detection of chemical stimulus involved in sensory perception of pain / TRP channels / smooth muscle contraction involved in micturition ...negative regulation of establishment of blood-brain barrier / response to capsazepine / sensory perception of mechanical stimulus / peptide secretion / cellular response to temperature stimulus / excitatory extracellular ligand-gated monoatomic ion channel activity / temperature-gated ion channel activity / detection of chemical stimulus involved in sensory perception of pain / TRP channels / smooth muscle contraction involved in micturition / fever generation / urinary bladder smooth muscle contraction / thermoception / detection of temperature stimulus involved in thermoception / cellular response to acidic pH / negative regulation of systemic arterial blood pressure / response to pH / chloride channel regulator activity / dendritic spine membrane / glutamate secretion / monoatomic cation transmembrane transporter activity / cellular response to ATP / negative regulation of heart rate / ligand-gated monoatomic ion channel activity / response to pain / cellular response to alkaloid / temperature homeostasis / diet induced thermogenesis / cellular response to cytokine stimulus / detection of temperature stimulus involved in sensory perception of pain / intracellularly gated calcium channel activity / behavioral response to pain / negative regulation of mitochondrial membrane potential / calcium ion import across plasma membrane / monoatomic cation channel activity / extracellular ligand-gated monoatomic ion channel activity / sensory perception of pain / phosphatidylinositol binding / phosphoprotein binding / microglial cell activation / cellular response to nerve growth factor stimulus / GABA-ergic synapse / calcium ion transmembrane transport / calcium channel activity / cellular response to growth factor stimulus / response to peptide hormone / lipid metabolic process / positive regulation of nitric oxide biosynthetic process / calcium ion transport / transmembrane signaling receptor activity / cellular response to tumor necrosis factor / sensory perception of taste / cellular response to heat / positive regulation of cytosolic calcium ion concentration / response to heat / monoatomic ion transmembrane transport / protein homotetramerization / postsynaptic membrane / calmodulin binding / neuron projection / positive regulation of apoptotic process / external side of plasma membrane / neuronal cell body / dendrite / negative regulation of transcription by RNA polymerase II / ATP binding / metal ion binding / identical protein binding / membrane / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.55 Å | |||||||||
![]() | Kwon DH / Zhang F | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Heat-dependent opening of TRPV1 in the presence of capsaicin. Authors: Do Hoon Kwon / Feng Zhang / Yang Suo / Jonathan Bouvette / Mario J Borgnia / Seok-Yong Lee / ![]() Abstract: Transient receptor potential vanilloid member 1 (TRPV1) is a Ca-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. Using cryo-EM, we have determined the ...Transient receptor potential vanilloid member 1 (TRPV1) is a Ca-permeable cation channel that serves as the primary heat and capsaicin sensor in humans. Using cryo-EM, we have determined the structures of apo and capsaicin-bound full-length rat TRPV1 reconstituted into lipid nanodiscs over a range of temperatures. This has allowed us to visualize the noxious heat-induced opening of TRPV1 in the presence of capsaicin. Notably, noxious heat-dependent TRPV1 opening comprises stepwise conformational transitions. Global conformational changes across multiple subdomains of TRPV1 are followed by the rearrangement of the outer pore, leading to gate opening. Solvent-accessible surface area analyses and functional studies suggest that a subset of residues form an interaction network that is directly involved in heat sensing. Our study provides a glimpse of the molecular principles underlying noxious physical and chemical stimuli sensing by TRPV1, which can be extended to other thermal sensing ion channels. | |||||||||
History |
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Structure visualization
Movie |
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Structure viewer | EM map: ![]() ![]() ![]() |
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 32.7 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 19.3 KB 19.3 KB | Display Display | ![]() |
Images | ![]() | 29.8 KB | ||
Filedesc metadata | ![]() | 6.7 KB | ||
Others | ![]() ![]() | 58.9 MB 58.9 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Validation report
Summary document | ![]() | 1 MB | Display | ![]() |
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Full document | ![]() | 1 MB | Display | |
Data in XML | ![]() | 12.4 KB | Display | |
Data in CIF | ![]() | 14.6 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7lpdMC ![]() 7lp9C ![]() 7lpaC ![]() 7lpbC ![]() 7lpcC ![]() 7lpeC M: atomic model generated by this map C: citing same article ( |
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Similar structure data |
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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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Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 1.059 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: half map 1
File | emd_23478_half_map_1.map | ||||||||||||
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Annotation | half map 1 | ||||||||||||
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Density Histograms |
-Half map: half map 2
File | emd_23478_half_map_2.map | ||||||||||||
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Annotation | half map 2 | ||||||||||||
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Density Histograms |
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Sample components
-Entire : Transient receptor potential cation channel subfamily V member 1
Entire | Name: Transient receptor potential cation channel subfamily V member 1 |
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Components |
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-Supramolecule #1: Transient receptor potential cation channel subfamily V member 1
Supramolecule | Name: Transient receptor potential cation channel subfamily V member 1 type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 400 KDa |
-Macromolecule #1: Transient receptor potential cation channel subfamily V member 1
Macromolecule | Name: Transient receptor potential cation channel subfamily V member 1 type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: ![]() ![]() |
Molecular weight | Theoretical: 98.719758 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: MEQRASLDSE ESESPPQENS CLDPPDRDPN CKPPPVKPHI FTTRSRTRLF GKGDSEEASP LDCPYEEGGL ASCPIITVSS VLTIQRPGD GPASVRPSSQ DSVSAGEKPP RLYDRRSIFD AVAQSNCQEL ESLLPFLQRS KKRLTDSEFK DPETGKTCLL K AMLNLHNG ...String: MEQRASLDSE ESESPPQENS CLDPPDRDPN CKPPPVKPHI FTTRSRTRLF GKGDSEEASP LDCPYEEGGL ASCPIITVSS VLTIQRPGD GPASVRPSSQ DSVSAGEKPP RLYDRRSIFD AVAQSNCQEL ESLLPFLQRS KKRLTDSEFK DPETGKTCLL K AMLNLHNG QNDTIALLLD VARKTDSLKQ FVNASYTDSY YKGQTALHIA IERRNMTLVT LLVENGADVQ AAANGDFFKK TK GRPGFYF GELPLSLAAC TNQLAIVKFL LQNSWQPADI SARDSVGNTV LHALVEVADN TVDNTKFVTS MYNEILILGA KLH PTLKLE EITNRKGLTP LALAASSGKI GVLAYILQRE IHEPECRHLS RKFTEWAYGP VHSSLYDLSC IDTCEKNSVL EVIA YSSSE TPNRHDMLLV EPLNRLLQDK WDRFVKRIFY FNFFVYCLYM IIFTAAAYYR PVEGLPPYKL KNTVGDYFRV TGEIL SVSG GVYFFFRGIQ YFLQRRPSLK SLFVDSYSEI LFFVQSLFML VSVVLYFSQR KEYVASMVFS LAMGWTNMLY YTRGFQ QMG IYAVMIEKMI LRDLCRFMFV YLVFLFGFST AVVTLIEDGK NNSLPMESTP HKCRGSACKP GNSYNSLYST CLELFKF TI GMGDLEFTEN YDFKAVFIIL LLAYVILTYI LLLNMLIALM GETVNKIAQE SKNIWKLQRA ITILDTEKSF LKCMRKAF R SGKLLQVGFT PDGKDDYRWC FRVDEVNWTT WNTNVGIINE DPGNCEGVKR TLSFSLRSGR VSGRNWKNFA LVPLLRDAS TRDRHATQQE EVQLKHYTGS LKPEDAEVFK DSMVPGEKEN SLEVLFQGPD YKDDDDKAHH HHHHHHHH UniProtKB: Transient receptor potential cation channel subfamily V member 1 |
-Macromolecule #2: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine
Macromolecule | Name: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine / type: ligand / ID: 2 / Number of copies: 8 / Formula: LBN |
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Molecular weight | Theoretical: 760.076 Da |
Chemical component information | ![]() ChemComp-LBN: |
-Macromolecule #3: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyl...
Macromolecule | Name: [(2~{R})-1-[2-azanylethoxy(oxidanyl)phosphoryl]oxy-3-hexadecanoyloxy-propan-2-yl] (~{Z})-octadec-9-enoate type: ligand / ID: 3 / Number of copies: 12 / Formula: 6OU |
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Molecular weight | Theoretical: 717.996 Da |
Chemical component information | ![]() ChemComp-6OU: |
-Macromolecule #4: (6E)-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide
Macromolecule | Name: (6E)-N-(4-hydroxy-3-methoxybenzyl)-8-methylnon-6-enamide type: ligand / ID: 4 / Number of copies: 4 / Formula: 4DY |
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Molecular weight | Theoretical: 305.412 Da |
Chemical component information | ![]() ChemComp-4DY: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Concentration | 1.0 mg/mL | ||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: Quantifoil / Material: GOLD / Mesh: 300 / Support film - Material: GOLD / Support film - topology: HOLEY | ||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 85 % / Chamber temperature: 321 K / Instrument: LEICA EM GP |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Specialist optics | Energy filter - Name: GIF Bioquantum / Energy filter - Slit width: 20 eV |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Digitization - Dimensions - Width: 5760 pixel / Digitization - Dimensions - Height: 4092 pixel / Number grids imaged: 1 / Number real images: 3744 / Average exposure time: 4.0 sec. / Average electron dose: 50.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 50.0 µm / Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Cs: 2.7 mm / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm / Nominal magnification: 81000 |
Sample stage | Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER / Cooling holder cryogen: NITROGEN |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
-Atomic model buiding 1
Initial model | PDB ID: Chain - Chain ID: A / Chain - Source name: PDB / Chain - Initial model type: experimental model |
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Refinement | Space: REAL / Protocol: FLEXIBLE FIT / Overall B value: 120 |
Output model | ![]() PDB-7lpd: |