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Yorodumi- PDB-7l2w: cryo-EM structure of RTX-bound minimal TRPV1 with NMDG at state a -
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Basic information
| Entry | Database: PDB / ID: 7l2w | ||||||||||||||||||
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| Title | cryo-EM structure of RTX-bound minimal TRPV1 with NMDG at state a | ||||||||||||||||||
Components | Transient receptor potential cation channel subfamily V member 1 | ||||||||||||||||||
Keywords | TRANSPORT PROTEIN / TRP channel / cryo-EM / nanodisc / large cation / vanilloid agonist | ||||||||||||||||||
| Function / homology | Function and homology informationnegative regulation of iodide transmembrane transport / negative regulation of establishment of blood-brain barrier / peptide secretion / sensory perception of mechanical stimulus / detection of temperature stimulus involved in thermoception / positive regulation of membrane depolarization / positive regulation of renal sodium excretion / response to capsazepine / cellular response to temperature stimulus / detection of chemical stimulus involved in sensory perception of pain ...negative regulation of iodide transmembrane transport / negative regulation of establishment of blood-brain barrier / peptide secretion / sensory perception of mechanical stimulus / detection of temperature stimulus involved in thermoception / positive regulation of membrane depolarization / positive regulation of renal sodium excretion / response to capsazepine / cellular response to temperature stimulus / detection of chemical stimulus involved in sensory perception of pain / positive regulation of sensory perception of pain / temperature-gated ion channel activity / smooth muscle contraction involved in micturition / TRP channels / fever generation / negative regulation of axon regeneration / diet induced thermogenesis / positive regulation of cardiac muscle cell differentiation / urinary bladder smooth muscle contraction / thermoception / response to pH / glutamate secretion / monoatomic cation transmembrane transporter activity / response to acidic pH / negative regulation of systemic arterial blood pressure / response to pain / excitatory extracellular ligand-gated monoatomic ion channel activity / dendritic spine membrane / positive regulation of urine volume / negative regulation of heart rate / cellular response to alkaloid / cellular response to cytokine stimulus / sensory perception of taste / temperature homeostasis / intracellularly gated calcium channel activity / cellular response to ATP / negative regulation of mitochondrial membrane potential / detection of temperature stimulus involved in sensory perception of pain / behavioral response to pain / calcium ion import across plasma membrane / positive regulation of vasoconstriction / monoatomic ion channel activity / ligand-gated monoatomic ion channel activity / monoatomic cation channel activity / cellular response to acidic pH / extracellular ligand-gated monoatomic ion channel activity / sensory perception of pain / phosphatidylinositol binding / axon terminus / positive regulation of excitatory postsynaptic potential / lipid metabolic process / sarcoplasmic reticulum / microglial cell activation / phosphoprotein binding / cellular response to tumor necrosis factor / cellular response to nerve growth factor stimulus / cellular response to growth factor stimulus / response to peptide hormone / GABA-ergic synapse / calcium ion transmembrane transport / calcium channel activity / positive regulation of nitric oxide biosynthetic process / calcium ion transport / transmembrane signaling receptor activity / cellular response to heat / response to heat / positive regulation of cytosolic calcium ion concentration / monoatomic ion transmembrane transport / protein homotetramerization / calmodulin binding / postsynaptic membrane / 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 / membrane / metal ion binding / identical protein binding / nucleus / plasma membrane Similarity search - Function | ||||||||||||||||||
| Biological species | ![]() | ||||||||||||||||||
| Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.16 Å | ||||||||||||||||||
Authors | Zhang, K. / Julius, D. / Cheng, Y. | ||||||||||||||||||
| Funding support | France, United States, 5items
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Citation | Journal: Cell / Year: 2021Title: Structural snapshots of TRPV1 reveal mechanism of polymodal functionality. Authors: Kaihua Zhang / David Julius / Yifan Cheng / ![]() Abstract: Many transient receptor potential (TRP) channels respond to diverse stimuli and conditionally conduct small and large cations. Such functional plasticity is presumably enabled by a uniquely dynamic ...Many transient receptor potential (TRP) channels respond to diverse stimuli and conditionally conduct small and large cations. Such functional plasticity is presumably enabled by a uniquely dynamic ion selectivity filter that is regulated by physiological agents. What is currently missing is a "photo series" of intermediate structural states that directly address this hypothesis and reveal specific mechanisms behind such dynamic channel regulation. Here, we exploit cryoelectron microscopy (cryo-EM) to visualize conformational transitions of the capsaicin receptor, TRPV1, as a model to understand how dynamic transitions of the selectivity filter in response to algogenic agents, including protons, vanilloid agonists, and peptide toxins, permit permeation by small and large organic cations. These structures also reveal mechanisms governing ligand binding substates, as well as allosteric coupling between key sites that are proximal to the selectivity filter and cytoplasmic gate. These insights suggest a general framework for understanding how TRP channels function as polymodal signal integrators. | ||||||||||||||||||
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Structure visualization
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| Structure viewer | Molecule: Molmil Jmol/JSmol |
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Downloads & links
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Download
| PDBx/mmCIF format | 7l2w.cif.gz | 391.1 KB | Display | PDBx/mmCIF format |
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| PDB format | pdb7l2w.ent.gz | 320.7 KB | Display | PDB format |
| PDBx/mmJSON format | 7l2w.json.gz | Tree view | PDBx/mmJSON format | |
| Others | Other downloads |
-Validation report
| Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/l2/7l2w ftp://data.pdbj.org/pub/pdb/validation_reports/l2/7l2w | HTTPS FTP |
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-Related structure data
| Related structure data | ![]() 23143MC ![]() 7l2hC ![]() 7l2iC ![]() 7l2jC ![]() 7l2kC ![]() 7l2lC ![]() 7l2mC ![]() 7l2nC ![]() 7l2oC ![]() 7l2pC ![]() 7l2rC ![]() 7l2sC ![]() 7l2tC ![]() 7l2uC ![]() 7l2vC ![]() 7l2xC ![]() 7mz5C ![]() 7mz6C ![]() 7mz7C ![]() 7mz9C ![]() 7mzaC ![]() 7mzbC ![]() 7mzcC ![]() 7mzdC ![]() 7mzeC M: map data used to model this data C: citing same article ( |
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| Similar structure data |
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Links
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Assembly
| Deposited unit | ![]()
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Components
| #1: Protein | Mass: 73016.352 Da / Num. of mol.: 4 Source method: isolated from a genetically manipulated source Source: (gene. exp.) ![]() Homo sapiens (human) / References: UniProt: O35433#2: Chemical | ChemComp-6EU / #3: Chemical | ChemComp-6IY / ( #4: Chemical | ChemComp-NA / | #5: Water | ChemComp-HOH / | Has ligand of interest | 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: minimal TRPV1 in nanodisc / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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| Source (natural) | Organism: ![]() |
| Source (recombinant) | Organism: Homo sapiens (human) |
| Buffer solution | pH: 6.82 |
| Specimen | Embedding applied: YES / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
| EM embedding | Material: nanodisc |
| Vitrification | Cryogen name: ETHANE |
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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: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
| Electron lens | Mode: BRIGHT FIELD |
| Image recording | Electron dose: 68.4 e/Å2 / Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) |
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Processing
| CTF correction | Type: NONE |
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| 3D reconstruction | Resolution: 3.16 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 26158 / Symmetry type: POINT |
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France,
United States, 5items
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