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Open data
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Basic information
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Title | TRPV1 in nanodisc bound with PI-Br4, consensus structure![]() | |||||||||
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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 / excitatory extracellular ligand-gated monoatomic ion channel activity / 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 / negative regulation of establishment of blood-brain barrier / sensory perception of mechanical stimulus / peptide secretion / excitatory extracellular ligand-gated monoatomic ion channel activity / 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 / ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() ![]() Similarity search - Function | |||||||||
Biological species | ![]() ![]() ![]() | |||||||||
Method | ![]() ![]() | |||||||||
![]() | Arnold WR / Julius D / Cheng Y | |||||||||
Funding support | ![]()
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![]() | ![]() 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 | ![]() | 258.9 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 15 KB 15 KB | Display Display | ![]() |
FSC (resolution estimation) | ![]() | 14.4 KB | Display | ![]() |
Images | ![]() | 74.6 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Others | ![]() ![]() | 254.4 MB 254.4 MB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 8u4dMC ![]() 8t0cC ![]() 8t0eC ![]() 8t0yC ![]() 8t10C ![]() 8t3lC ![]() 8t3mC ![]() 8u2zC ![]() 8u30C ![]() 8u3aC ![]() 8u3cC ![]() 8u3jC ![]() 8u3lC ![]() 8u43C M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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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: 0.644 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
-Half map: #2
File | emd_41879_half_map_1.map | ||||||||||||
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Projections & Slices |
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Density Histograms |
-Half map: #1
File | emd_41879_half_map_2.map | ||||||||||||
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Density Histograms |
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Sample components
-Entire : TRPV1 in nanodisc bound with PI-Br4, consensus structure
Entire | Name: TRPV1 in nanodisc bound with PI-Br4, consensus structure![]() |
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Components |
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-Supramolecule #1: TRPV1 in nanodisc bound with PI-Br4, consensus structure
Supramolecule | Name: TRPV1 in nanodisc bound with PI-Br4, consensus structure type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() ![]() ![]() |
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: ![]() ![]() ![]() |
Molecular weight | Theoretical: 72.888227 KDa |
Recombinant expression | Organism: ![]() ![]() |
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: ![]() |
-Macromolecule #2: (2S)-2-[(9,10-dibromooctadecanoyl)oxy]-3-{[(S)-hydroxy{[(1S,2R,3R...
Macromolecule | Name: (2S)-2-[(9,10-dibromooctadecanoyl)oxy]-3-{[(S)-hydroxy{[(1S,2R,3R,4S,5S,6R)-2,3,4,5,6-pentahydroxycyclohexyl]oxy}phosphoryl]oxy}propyl (9R,10S)-9,10-dibromooctadecanoate type: ligand / ID: 2 / Number of copies: 4 / Formula: VPN |
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Molecular weight | Theoretical: 1.182722 KDa |
-Macromolecule #3: SODIUM ION
Macromolecule | Name: SODIUM ION / type: ligand / ID: 3 / Number of copies: 1 |
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Molecular weight | Theoretical: 22.99 Da |
-Macromolecule #4: water
Macromolecule | Name: water / type: ligand / ID: 4 / Number of copies: 2 / Formula: HOH |
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Molecular weight | Theoretical: 18.015 Da |
Chemical component information | ![]() ChemComp-HOH: |
-Experimental details
-Structure determination
Method | ![]() |
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Aggregation state | particle |
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Sample preparation
Concentration | 2.1 mg/mL |
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Buffer | pH: 7.5 |
Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD![]() |
Image recording | Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 47.2 e/Å2 |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |