+Open data
-Basic information
Entry | Database: EMDB / ID: EMD-41873 | |||||||||
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Title | TRPV1 in nanodisc bound with PIP2-Br4 | |||||||||
Map data | ||||||||||
Sample |
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Keywords | TRPV1 in nanodisc bound with PIP2-Br4 MEMBRANE PROTEIN / MEMBRANE PROTEIN | |||||||||
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 / 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 / fever generation / detection of temperature stimulus involved in thermoception / thermoception / negative regulation of systemic arterial blood pressure / glutamate secretion / chloride channel regulator activity / response to pH / dendritic spine membrane / monoatomic cation transmembrane transporter activity / excitatory extracellular ligand-gated monoatomic ion channel activity / negative regulation of heart rate / cellular response to ATP / temperature homeostasis / response to pain / cellular response to alkaloid / calcium ion import across plasma membrane / behavioral response to pain / diet induced thermogenesis / cellular response to cytokine stimulus / detection of temperature stimulus involved in sensory perception of pain / intracellularly gated calcium channel activity / negative regulation of mitochondrial membrane potential / ligand-gated monoatomic ion channel activity / extracellular ligand-gated monoatomic ion channel activity / monoatomic cation channel activity / GABA-ergic synapse / 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 / calcium ion transport / positive regulation of nitric oxide biosynthetic process / transmembrane signaling receptor activity / cellular response to tumor necrosis factor / cellular response to heat / positive regulation of cytosolic calcium ion concentration / response to heat / monoatomic ion transmembrane transport / 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 | single particle reconstruction / cryo EM / Resolution: 2.4 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_41873.map.gz | 258.9 MB | EMDB map data format | |
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Header (meta data) | emd-41873-v30.xml emd-41873.xml | 15.3 KB 15.3 KB | Display Display | EMDB header |
FSC (resolution estimation) | emd_41873_fsc.xml | 14.3 KB | Display | FSC data file |
Images | emd_41873.png | 88.9 KB | ||
Filedesc metadata | emd-41873.cif.gz | 6 KB | ||
Others | emd_41873_half_map_1.map.gz emd_41873_half_map_2.map.gz | 254.1 MB 254.1 MB | ||
Archive directory | http://ftp.pdbj.org/pub/emdb/structures/EMD-41873 ftp://ftp.pdbj.org/pub/emdb/structures/EMD-41873 | HTTPS FTP |
-Validation report
Summary document | emd_41873_validation.pdf.gz | 763 KB | Display | EMDB validaton report |
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Full document | emd_41873_full_validation.pdf.gz | 762.5 KB | Display | |
Data in XML | emd_41873_validation.xml.gz | 22.5 KB | Display | |
Data in CIF | emd_41873_validation.cif.gz | 29.4 KB | Display | |
Arichive directory | https://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41873 ftp://ftp.pdbj.org/pub/emdb/validation_reports/EMD-41873 | HTTPS FTP |
-Related structure data
Related structure data | 8u43MC 8t0cC 8t0eC 8t0yC 8t10C 8t3lC 8t3mC 8u2zC 8u30C 8u3aC 8u3cC 8u3jC 8u3lC 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_41873.map.gz / Format: CCP4 / Size: 274.6 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES) | ||||||||||||||||||||||||||||||||||||
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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: #2
File | emd_41873_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_41873_half_map_2.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Sample components
-Entire : TRPV1 in nanodisc bound with PIP2-Br4
Entire | Name: TRPV1 in nanodisc bound with PIP2-Br4 |
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Components |
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-Supramolecule #1: TRPV1 in nanodisc bound with PIP2-Br4
Supramolecule | Name: TRPV1 in nanodisc bound with PIP2-Br4 / 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 / Number of copies: 4 / Enantiomer: LEVO |
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Source (natural) | Organism: Rattus norvegicus (Norway rat) |
Molecular weight | Theoretical: 72.888227 KDa |
Recombinant expression | Organism: Homo sapiens (human) |
Sequence | String: MGSRLYDRRS IFDAVAQSNC QELESLLPFL QRSKKRLTDS EFKDPETGKT CLLKAMLNLH NGQNDTIALL LDVARKTDSL KQFVNASYT DSYYKGQTAL HIAIERRNMT LVTLLVENGA DVQAAANGDF FKKTKGRPGF YFGELPLSLA ACTNQLAIVK F LLQNSWQP ...String: MGSRLYDRRS IFDAVAQSNC QELESLLPFL QRSKKRLTDS EFKDPETGKT CLLKAMLNLH NGQNDTIALL LDVARKTDSL KQFVNASYT DSYYKGQTAL HIAIERRNMT LVTLLVENGA DVQAAANGDF FKKTKGRPGF YFGELPLSLA ACTNQLAIVK F LLQNSWQP ADISARDSVG NTVLHALVEV ADNTVDNTKF VTSMYNEILI LGAKLHPTLK LEEITNRKGL TPLALAASSG KI GVLAYIL QREIHEPECR HLSRKFTEWA YGPVHSSLYD LSCIDTCEKN SVLEVIAYSS SETPNRHDML LVEPLNRLLQ DKW DRFVKR IFYFNFFVYC LYMIIFTAAA YYRPVEGLPP YKLKNTVGDY FRVTGEILSV SGGVYFFFRG IQYFLQRRPS LKSL FVDSY SEILFFVQSL FMLVSVVLYF SQRKEYVASM VFSLAMGWTN MLYYTRGFQQ MGIYAVMIEK MILRDLCRFM FVYLV FLFG FSTAVVTLIE DGKYNSLYST CLELFKFTIG MGDLEFTENY DFKAVFIILL LAYVILTYIL LLNMLIALMG ETVNKI AQE SKNIWKLQRA ITILDTEKSF LKCMRKAFRS GKLLQVGFTP DGKDDYRWCF RVDEVNWTTW NTNVGIINED PG UniProtKB: Transient receptor potential cation channel subfamily V member 1 |
-Macromolecule #2: (2S)-2-[(9,10-dibromooctadecanoyl)oxy]-3-{[(S)-hydroxy{[(1R,2R,3S...
Macromolecule | Name: (2S)-2-[(9,10-dibromooctadecanoyl)oxy]-3-{[(S)-hydroxy{[(1R,2R,3S,4R,5R,6S)-2,3,6-trihydroxy-4,5-bis(phosphonooxy)cyclohexyl]oxy}phosphoryl]oxy}propyl (9R,10S)-9,10-dibromooctadecanoate type: ligand / ID: 2 / Number of copies: 4 / Formula: V5H |
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Molecular weight | Theoretical: 1.342682 KDa |
-Macromolecule #3: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
Macromolecule | Name: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 3 / Number of copies: 4 / Formula: PCW |
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Molecular weight | Theoretical: 787.121 Da |
Chemical component information | ChemComp-PCW: |
-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 |
-Macromolecule #5: water
Macromolecule | Name: water / type: ligand / ID: 5 / Number of copies: 130 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ChemComp-HOH: |
-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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Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 45.8 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 0.8 µm |
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |