+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41006 | |||||||||
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Title | TRPV1 in nanodisc bound with 3 LPA molecules | |||||||||
Map data | TRPV1 in nanodisc bound with 3 LPA molecules | |||||||||
Sample |
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Keywords | TRPV1 / lysophosphatidic acid / MEMBRANE PROTEIN | |||||||||
Function / homology | Function and homology information temperature-gated ion channel activity / response to capsazepine / excitatory extracellular ligand-gated monoatomic ion channel activity / 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 ...temperature-gated ion channel activity / response to capsazepine / excitatory extracellular ligand-gated monoatomic ion channel activity / 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 / thermoception / fever generation / detection of temperature stimulus involved in thermoception / glutamate secretion / dendritic spine membrane / negative regulation of systemic arterial blood pressure / chloride channel regulator activity / response to pH / monoatomic cation transmembrane transporter activity / cellular response to ATP / response to pain / temperature homeostasis / negative regulation of heart rate / cellular response to alkaloid / behavioral response to pain / diet induced thermogenesis / extracellular ligand-gated monoatomic ion channel activity / intracellularly gated calcium channel activity / cellular response to cytokine stimulus / negative regulation of mitochondrial membrane potential / detection of temperature stimulus involved in sensory perception of pain / calcium ion import across plasma membrane / ligand-gated monoatomic ion channel activity / monoatomic cation channel activity / sensory perception of pain / response to organonitrogen compound / phosphatidylinositol binding / monoatomic ion transmembrane transport / cellular response to nerve growth factor stimulus / phosphoprotein binding / calcium ion transmembrane transport / microglial cell activation / calcium channel activity / lipid metabolic process / response to peptide hormone / cellular response to growth factor stimulus / positive regulation of nitric oxide biosynthetic process / calcium ion transport / transmembrane signaling receptor activity / cellular response to heat / cellular response to tumor necrosis factor / 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 / membrane / identical protein binding / metal ion binding / plasma membrane Similarity search - Function | |||||||||
Biological species | Rattus norvegicus (Norway rat) | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.5 Å | |||||||||
Authors | Arnold WR / Julius D / Cheng Y | |||||||||
Funding support | United States, 2 items
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Citation | Journal: Nat Struct Mol Biol / Year: 2024 Title: Structural basis of TRPV1 modulation by endogenous bioactive lipids. Authors: William R Arnold / Adamo Mancino / Frank R Moss / Adam Frost / David Julius / Yifan Cheng / Abstract: TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for ...TRP ion channels are modulated by phosphoinositide lipids, but the underlying structural mechanisms remain unclear. The capsaicin- and heat-activated receptor, TRPV1, has served as a model for deciphering lipid modulation, which is relevant to understanding how pro-algesic agents enhance channel activity in the setting of inflammatory pain. Identification of a pocket within the TRPV1 transmembrane core has provided initial clues as to how phosphoinositide lipids bind to and regulate the channel. Here we show that this regulatory pocket in rat TRPV1 can accommodate diverse lipid species, including the inflammatory lipid lysophosphatidic acid, whose actions are determined by their specific modes of binding. Furthermore, we show that an empty-pocket channel lacking an endogenous phosphoinositide lipid assumes an agonist-like state, even at low temperature, substantiating the concept that phosphoinositide lipids serve as negative TRPV1 modulators whose ejection from the binding pocket is a critical step toward activation by thermal or chemical stimuli. | |||||||||
History |
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-Structure visualization
Supplemental images |
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-Downloads & links
-EMDB archive
Map data | emd_41006.map.gz | 12.2 MB | EMDB map data format | |
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Header (meta data) | emd-41006-v30.xml emd-41006.xml | 15.4 KB 15.4 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41006_fsc.xml | 13.7 KB | Display | FSC data file |
Images | emd_41006.png | 44.8 KB | ||
Filedesc metadata | emd-41006.cif.gz | 6 KB | ||
Others | emd_41006_half_map_1.map.gz emd_41006_half_map_2.map.gz | 171.4 MB 171.4 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41006 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41006 | HTTPS FTP |
-Related structure data
Related structure data | 8t3mMC 8t0cC 8t0eC 8t0yC 8t10C 8t3lC 8u2zC 8u30C 8u3aC 8u3cC 8u3jC 8u3lC 8u43C 8u4dC M: atomic model generated by this map C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
EMDB pages | EMDB (EBI/PDBe) / EMDataResource |
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Related items in Molecule of the Month |
-Map
File | Download / File: emd_41006.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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Annotation | TRPV1 in nanodisc bound with 3 LPA molecules | ||||||||||||||||||||||||||||||||||||
Projections & slices | Image control
Images are generated by Spider. | ||||||||||||||||||||||||||||||||||||
Voxel size | X=Y=Z: 0.835 Å | ||||||||||||||||||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: Half Map A for TRPV1 in nanodisc bound with 3 LPA molecules
File | emd_41006_half_map_1.map | ||||||||||||
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Annotation | Half Map A for TRPV1 in nanodisc bound with 3 LPA molecules | ||||||||||||
Projections & Slices |
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Density Histograms |
-Half map: Half Map B for TRPV1 in nanodisc bound with 3 LPA molecules
File | emd_41006_half_map_2.map | ||||||||||||
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Annotation | Half Map B for TRPV1 in nanodisc bound with 3 LPA molecules | ||||||||||||
Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TRPV1 in nanodisc bound with 2 LPA molecules in neighboring monomers
Entire | Name: TRPV1 in nanodisc bound with 2 LPA molecules in neighboring monomers |
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Components |
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-Supramolecule #1: TRPV1 in nanodisc bound with 2 LPA molecules in neighboring monomers
Supramolecule | Name: TRPV1 in nanodisc bound with 2 LPA molecules in neighboring monomers type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 688 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 / Details: Truncated TRPV1 from Rattus norvegicus / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 73.016352 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
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 UniProtKB: Transient receptor potential cation channel subfamily V member 1 |
-Macromolecule #2: [(2~{R})-2-hexadecanoyloxy-3-[oxidanyl-[(2~{S},3~{S},5~{R},6~{S})...
Macromolecule | Name: [(2~{R})-2-hexadecanoyloxy-3-[oxidanyl-[(2~{S},3~{S},5~{R},6~{S})-2,3,4,5,6-pentakis(oxidanyl)cyclohexyl]oxy-phosphoryl]oxy-propyl] hexadecanoate type: ligand / ID: 2 / Number of copies: 1 / Formula: 85R |
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Molecular weight | Theoretical: 811.032 Da |
Chemical component information | ChemComp-85R: |
-Macromolecule #3: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 3 / Number of copies: 2 |
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Molecular weight | Theoretical: 22.99 Da |
-Macromolecule #4: (2R)-2-hydroxy-3-(phosphonooxy)propyl tetradecanoate
Macromolecule | Name: (2R)-2-hydroxy-3-(phosphonooxy)propyl tetradecanoate / type: ligand / ID: 4 / Number of copies: 3 / Formula: NKN |
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Molecular weight | Theoretical: 382.429 Da |
Chemical component information | ChemComp-NKN: |
-Experimental details
-Structure determination
Method | cryo EM |
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Processing | single particle reconstruction |
Aggregation state | particle |
-Sample preparation
Concentration | 2.1 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELDBright-field microscopy / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 45.8 e/Å2 |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |