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Yorodumi- PDB-7rqy: Cryo-EM structure of the full-length TRPV1 with RTx at 25 degrees... -
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-Basic information
Entry | Database: PDB / ID: 7rqy | ||||||
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Title | Cryo-EM structure of the full-length TRPV1 with RTx at 25 degrees Celsius, in an open state, class B | ||||||
Components | Transient receptor potential cation channel subfamily V member 1 | ||||||
Keywords | MEMBRANE PROTEIN / ligand-gating ion channel | ||||||
Function / homology | Function and homology information 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 / cellular response to temperature stimulus / smooth muscle contraction involved in micturition / TRP channels ...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 / cellular response to temperature stimulus / smooth muscle contraction involved in micturition / TRP channels / cellular response to acidic pH / excitatory extracellular ligand-gated monoatomic ion channel activity / thermoception / fever generation / 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 / extracellular ligand-gated monoatomic ion channel activity / cellular response to ATP / negative regulation of heart rate / temperature homeostasis / response to pain / cellular response to alkaloid / behavioral response to pain / diet induced thermogenesis / 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 / calcium ion import across plasma membrane / monoatomic cation channel activity / monoatomic ion transmembrane transport / sensory perception of pain / : / phosphatidylinositol binding / cellular response to nerve growth factor stimulus / calcium ion transmembrane transport / phosphoprotein binding / 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 / cellular response to heat / positive regulation of cytosolic calcium ion concentration / 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 | Rattus norvegicus (Norway rat) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.04 Å | ||||||
Authors | Kwon, D.H. / Suo, Y. / Lee, S.-Y. | ||||||
Funding support | United States, 1items
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Citation | Journal: Nat Commun / Year: 2022 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
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7rqy.cif.gz | 694.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7rqy.ent.gz | 588.9 KB | Display | PDB format |
PDBx/mmJSON format | 7rqy.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7rqy_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 7rqy_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 7rqy_validation.xml.gz | 65.3 KB | Display | |
Data in CIF | 7rqy_validation.cif.gz | 91.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/rq/7rqy ftp://data.pdbj.org/pub/pdb/validation_reports/rq/7rqy | HTTPS FTP |
-Related structure data
Related structure data | 24640MC 7rquC 7rqvC 7rqwC 7rqxC 7rqzC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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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.) Rattus norvegicus (Norway rat) / Gene: Trpv1, Vr1, Vr1l / Production host: Homo sapiens (human) / References: UniProt: O35433 #2: Chemical | ChemComp-6EU / #3: Chemical | ChemComp-LBN / #4: Chemical | ChemComp-6OU / [( Has ligand of interest | N | |
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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 |
-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: Rattus norvegicus (Norway rat) | ||||||||||||
Source (recombinant) | Organism: Homo sapiens (human) | ||||||||||||
Buffer solution | pH: 7.5 | ||||||||||||
Buffer component |
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Specimen | Conc.: 0.8 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: 298 K |
-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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
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: 4023 |
EM imaging optics | Energyfilter name: GIF Bioquantum / Energyfilter slit width: 20 eV |
Image scans | Width: 5760 / Height: 4092 |
-Processing
EM software |
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||||||||||||||
Particle selection | Num. of particles selected: 2700 | ||||||||||||||||||||||||||||||||||||
3D reconstruction | Resolution: 3.04 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 104123 / Symmetry type: POINT | ||||||||||||||||||||||||||||||||||||
Atomic model building | B value: 116 / Protocol: FLEXIBLE FIT / Space: REAL | ||||||||||||||||||||||||||||||||||||
Atomic model building | PDB-ID: 7LP9 Pdb chain-ID: A |