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- EMDB-24637: Cryo-EM structure of the full-length TRPV1 with RTx at 4 degrees ... -
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Open data
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Basic information
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Title | Cryo-EM structure of the full-length TRPV1 with RTx at 4 degrees Celsius, in an intermediate-closed state, class II | |||||||||
![]() | 4C_RTX_inter | |||||||||
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Function / homology | ![]() temperature-gated ion channel activity / response to capsazepine / negative regulation of establishment of blood-brain barrier / sensory perception of mechanical stimulus / peptide secretion / urinary bladder smooth muscle contraction / detection of chemical stimulus involved in sensory perception of pain / smooth muscle contraction involved in micturition / TRP channels / cellular response to temperature stimulus ...temperature-gated ion channel activity / response to capsazepine / negative regulation of establishment of blood-brain barrier / sensory perception of mechanical stimulus / peptide secretion / urinary bladder smooth muscle contraction / detection of chemical stimulus involved in sensory perception of pain / smooth muscle contraction involved in micturition / TRP channels / cellular response to temperature stimulus / cellular response to acidic pH / excitatory extracellular ligand-gated monoatomic ion channel activity / fever generation / thermoception / detection of temperature stimulus involved in thermoception / glutamate secretion / negative regulation of systemic arterial blood pressure / chloride channel regulator activity / dendritic spine membrane / response to pH / monoatomic cation transmembrane transporter activity / cellular response to ATP / negative regulation of heart rate / temperature homeostasis / response to pain / cellular response to alkaloid / calcium ion import across plasma membrane / diet induced thermogenesis / behavioral response to pain / intracellularly gated calcium channel activity / cellular response to cytokine stimulus / detection of temperature stimulus involved in sensory perception of pain / negative regulation of mitochondrial membrane potential / ligand-gated monoatomic ion channel activity / extracellular ligand-gated monoatomic ion channel activity / monoatomic cation channel activity / monoatomic ion transmembrane transport / sensory perception of pain / : / phosphatidylinositol binding / cellular response to nerve growth factor stimulus / phosphoprotein binding / calcium ion transmembrane transport / microglial cell activation / calcium channel activity / lipid metabolic process / cellular response to growth factor stimulus / response to peptide hormone / transmembrane signaling receptor activity / calcium ion transport / positive regulation of nitric oxide biosynthetic process / cellular response to tumor necrosis factor / positive regulation of cytosolic calcium ion concentration / cellular response to heat / response to heat / postsynaptic membrane / protein homotetramerization / 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 / identical protein binding / membrane / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | ![]() ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.45 Å | |||||||||
![]() | Kwon DH / Suo Y / Lee S-Y | |||||||||
Funding support | ![]()
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![]() | ![]() Title: Vanilloid-dependent TRPV1 opening trajectory from cryoEM ensemble analysis. Authors: Do Hoon Kwon / Feng Zhang / Justin G Fedor / Yang Suo / Seok-Yong Lee / ![]() Abstract: Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational ...Single particle cryo-EM often yields multiple protein conformations within a single dataset, but experimentally deducing the temporal relationship of these conformers within a conformational trajectory is not trivial. Here, we use thermal titration methods and cryo-EM in an attempt to obtain temporal resolution of the conformational trajectory of the vanilloid receptor TRPV1 with resiniferatoxin (RTx) bound. Based on our cryo-EM ensemble analysis, RTx binding to TRPV1 appears to induce intracellular gate opening first, followed by selectivity filter dilation, then pore loop rearrangement to reach the final open state. This apparent conformational wave likely arises from the concerted, stepwise, additive structural changes of TRPV1 over many subdomains. Greater understanding of the RTx-mediated long-range allostery of TRPV1 could help further the therapeutic potential of RTx, which is a promising drug candidate for pain relief associated with advanced cancer or knee arthritis. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 59.5 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 16.1 KB 16.1 KB | Display Display | ![]() |
Images | ![]() | 77 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7rqvMC ![]() 7rquC ![]() 7rqwC ![]() 7rqxC ![]() 7rqyC ![]() 7rqzC 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
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Annotation | 4C_RTX_inter | ||||||||||||||||||||
Voxel size | X=Y=Z: 1.08 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 : 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: ![]() ![]() |
Recombinant expression | 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 |
-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: 4 / 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: resiniferatoxin
Macromolecule | Name: resiniferatoxin / type: ligand / ID: 4 / Number of copies: 4 / Formula: 6EU |
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Molecular weight | Theoretical: 628.708 Da |
Chemical component information | ![]() ChemComp-6EU: |
-Macromolecule #5: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 5 / Number of copies: 2 |
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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 | 0.9 mg/mL | ||||||
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Buffer | pH: 7.5 Component:
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Grid | Model: UltrAuFoil R1.2/1.3 / Material: GOLD / Support film - Material: GOLD / Support film - topology: HOLEY | ||||||
Vitrification | Cryogen name: ETHANE / Chamber humidity: 90 % / Chamber temperature: 277 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: 2427 / Average exposure time: 4.0 sec. / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | C2 aperture diameter: 100.0 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 |