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Open data
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Basic information
Entry | Database: EMDB / ID: EMD-24086 | ||||||||||||||||||
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Title | Cryo-EM structure of minimal TRPV1 with 1 partially bound RTX | ||||||||||||||||||
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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: 3.18 Å | ||||||||||||||||||
![]() | Zhang K / Julius D / Cheng Y | ||||||||||||||||||
Funding support | ![]() ![]()
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![]() | ![]() Title: 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. | ||||||||||||||||||
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 | ![]() | 117.1 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 17.3 KB 17.3 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 10.2 KB | Display | ![]() |
Images | ![]() | 163 KB | ||
Others | ![]() ![]() | 98.3 MB 98.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7mz9MC ![]() 7l2hC ![]() 7l2iC ![]() 7l2jC ![]() 7l2kC ![]() 7l2lC ![]() 7l2mC ![]() 7l2nC ![]() 7l2oC ![]() 7l2pC ![]() 7l2rC ![]() 7l2sC ![]() 7l2tC ![]() 7l2uC ![]() 7l2vC ![]() 7l2wC ![]() 7l2xC ![]() 7mz5C ![]() 7mz6C ![]() 7mz7C ![]() 7mzaC ![]() 7mzbC ![]() 7mzcC ![]() 7mzdC ![]() 7mzeC C: citing same article ( M: atomic model generated by this map |
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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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Voxel size | X=Y=Z: 0.834 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
CCP4 map header:
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-Supplemental data
-Half map: #2
File | emd_24086_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_24086_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : minimal TRPV1 in nanodisc
Entire | Name: minimal TRPV1 in nanodisc |
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Components |
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-Supramolecule #1: minimal TRPV1 in nanodisc
Supramolecule | Name: minimal TRPV1 in nanodisc / type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() |
Recombinant expression | Organism: ![]() |
-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: 73.016352 KDa |
Recombinant expression | Organism: ![]() |
Sequence | String: GAMGSRLYDR RSIFDAVAQS NCQELESLLP FLQRSKKRLT DSEFKDPETG KTCLLKAMLN LHNGQNDTIA LLLDVARKTD SLKQFVNAS YTDSYYKGQT ALHIAIERRN MTLVTLLVEN GADVQAAANG DFFKKTKGRP GFYFGELPLS LAACTNQLAI V KFLLQNSW ...String: GAMGSRLYDR RSIFDAVAQS NCQELESLLP FLQRSKKRLT DSEFKDPETG KTCLLKAMLN LHNGQNDTIA LLLDVARKTD SLKQFVNAS YTDSYYKGQT ALHIAIERRN MTLVTLLVEN GADVQAAANG DFFKKTKGRP GFYFGELPLS LAACTNQLAI V KFLLQNSW QPADISARDS VGNTVLHALV EVADNTVDNT KFVTSMYNEI LILGAKLHPT LKLEEITNRK GLTPLALAAS SG KIGVLAY ILQREIHEPE CRHLSRKFTE WAYGPVHSSL YDLSCIDTCE KNSVLEVIAY SSSETPNRHD MLLVEPLNRL LQD KWDRFV KRIFYFNFFV YCLYMIIFTA AAYYRPVEGL PPYKLKNTVG DYFRVTGEIL SVSGGVYFFF RGIQYFLQRR PSLK SLFVD SYSEILFFVQ SLFMLVSVVL YFSQRKEYVA SMVFSLAMGW TNMLYYTRGF QQMGIYAVMI EKMILRDLCR FMFVY LVFL FGFSTAVVTL IEDGKYNSLY STCLELFKFT IGMGDLEFTE NYDFKAVFII LLLAYVILTY ILLLNMLIAL MGETVN KIA QESKNIWKLQ RAITILDTEK SFLKCMRKAF RSGKLLQVGF TPDGKDDYRW CFRVDEVNWT TWNTNVGIIN EDPG |
-Macromolecule #2: resiniferatoxin
Macromolecule | Name: resiniferatoxin / type: ligand / ID: 2 / Number of copies: 1 / Formula: 6EU |
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Molecular weight | Theoretical: 628.708 Da |
Chemical component information | ![]() ChemComp-6EU: |
-Macromolecule #3: (2S)-1-(butanoyloxy)-3-{[(R)-hydroxy{[(1r,2R,3S,4S,5R,6S)-2,3,4,5...
Macromolecule | Name: (2S)-1-(butanoyloxy)-3-{[(R)-hydroxy{[(1r,2R,3S,4S,5R,6S)-2,3,4,5,6-pentahydroxycyclohexyl]oxy}phosphoryl]oxy}propan-2-yl tridecanoate type: ligand / ID: 3 / Number of copies: 3 / Formula: XJ7 |
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Molecular weight | Theoretical: 600.633 Da |
Chemical component information | ![]() ChemComp-XJ7: |
-Macromolecule #4: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 4 / Number of copies: 1 |
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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
Buffer | pH: 6.85 |
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Sugar embedding | Material: nanodisc |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 66.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |