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- PDB-7rqz: Cryo-EM structure of the full-length TRPV1 with RTx at 48 degrees... -
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Basic information
Entry | Database: PDB / ID: 7rqz | ||||||
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Title | Cryo-EM structure of the full-length TRPV1 with RTx at 48 degrees Celsius, in an open state, class alpha | ||||||
![]() | Transient receptor potential cation channel subfamily V member 1 | ||||||
![]() | MEMBRANE PROTEIN / ligand-gating ion channel | ||||||
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 / detection of temperature stimulus involved in thermoception / thermoception / cellular response to acidic pH / negative regulation of systemic arterial blood pressure / chloride channel regulator activity / response to pH / 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 / calcium ion transmembrane transport / GABA-ergic synapse / cellular response to growth factor stimulus / calcium channel activity / 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 | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.32 Å | ||||||
![]() | Kwon, D.H. / 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. | ||||||
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Structure visualization
Structure viewer | Molecule: ![]() ![]() |
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Downloads & links
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PDBx/mmCIF format | ![]() | 718.3 KB | Display | ![]() |
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PDB format | ![]() | 588.8 KB | Display | ![]() |
PDBx/mmJSON format | ![]() | Tree view | ![]() | |
Others | ![]() |
-Validation report
Summary document | ![]() | 1.9 MB | Display | ![]() |
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Full document | ![]() | 2 MB | Display | |
Data in XML | ![]() | 67.2 KB | Display | |
Data in CIF | ![]() | 93.1 KB | Display | |
Arichive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 24641MC ![]() 7rquC ![]() 7rqvC ![]() 7rqwC ![]() 7rqxC ![]() 7rqyC M: map data used to model this data C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
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Assembly
Deposited unit | ![]()
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Components
#1: Protein | Mass: 98719.758 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() ![]() ![]() #2: Chemical | ChemComp-6EU / #3: Chemical | ChemComp-LBN / #4: Chemical | ChemComp-6OU / [( Has ligand of interest | N | Has protein modification | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
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Sample preparation
Component | Name: Transient receptor potential cation channel subfamily V member 1 Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT | ||||||||||||
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Molecular weight | Value: 0.4 MDa / Experimental value: NO | ||||||||||||
Source (natural) | Organism: ![]() ![]() | ||||||||||||
Source (recombinant) | Organism: ![]() | ||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||
Buffer component |
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Specimen | Conc.: 0.9 mg/ml / Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES | ||||||||||||
Specimen support | Grid type: UltrAuFoil R1.2/1.3 | ||||||||||||
Vitrification | Instrument: LEICA EM GP / Cryogen name: ETHANE / Humidity: 90 % / Chamber temperature: 321 K |
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Electron microscopy imaging
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: ![]() |
Electron lens | Mode: BRIGHT FIELD / Nominal magnification: 81000 X / Nominal defocus max: 1800 nm / Nominal defocus min: 800 nm / Cs: 2.7 mm / C2 aperture diameter: 100 µm / Alignment procedure: COMA FREE |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Average exposure time: 4 sec. / Electron dose: 44 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Num. of grids imaged: 1 / Num. of real images: 3042 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Width: 5760 / Height: 4092 |
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Processing
Software | Name: PHENIX / Version: 1.19.2_4158: / Classification: refinement | ||||||||||||||||||||||||||||||||
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EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 1500 | ||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.32 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 18341 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||
Atomic model building | B value: 116 / Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7LP9 Pdb chain-ID: A / Accession code: 7LP9 / Source name: PDB / Type: experimental model | ||||||||||||||||||||||||||||||||
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