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- EMDB-41847: TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state -

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Basic information

Entry
Database: EMDB / ID: EMD-41847
TitleTRPV1 in nanodisc bound with diC8-PIP2 in the dilated state
Map dataTRPV1 bound with diC8-PIP2 in the dilated state
Sample
  • Complex: TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state
    • Protein or peptide: Transient receptor potential cation channel subfamily V member 1
  • Ligand: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate
  • Ligand: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
  • Ligand: CHOLESTEROL
  • Ligand: SODIUM ION
  • Ligand: water
KeywordsTRPV1 in nanodisc bound with diC8-PIP2 in the dilated state / 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
Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeats (3 copies) / Ankyrin repeat profile. / Ankyrin repeat region circular profile. / ankyrin repeats / Ankyrin repeat / Ankyrin repeat-containing domain superfamily / Ion transport domain / Ion transport protein
Similarity search - Domain/homology
Transient receptor potential cation channel subfamily V member 1
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.6 Å
AuthorsArnold WR / Julius D / Cheng Y
Funding support United States, 2 items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS) United States
Howard Hughes Medical Institute (HHMI) United States
CitationJournal: 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
DepositionSep 6, 2023-
Header (metadata) releaseMay 8, 2024-
Map releaseMay 8, 2024-
UpdateOct 2, 2024-
Current statusOct 2, 2024Processing site: RCSB / Status: Released

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Structure visualization

Supplemental images

emd_41847.png

Downloads & links

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Map

FileDownload / File: emd_41847.map.gz / Format: CCP4 / Size: 216 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
AnnotationTRPV1 bound with diC8-PIP2 in the dilated state
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.84 Å/pix.
x 384 pix.
= 320.64 Å		0.84 Å/pix.
x 384 pix.
= 320.64 Å		0.84 Å/pix.
x 384 pix.
= 320.64 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.835 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.003
Minimum - Maximum-0.046465687 - 0.07708175
Average (Standard dev.)0.000018574425 (±0.0015955818)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions384384384
Spacing384384384
CellA=B=C: 320.63998 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: TRPV1 bound with diC8-PIP2 in the dilated state half map 1

Fileemd_41847_half_map_1.map
AnnotationTRPV1 bound with diC8-PIP2 in the dilated state half map 1
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: TRPV1 bound with diC8-PIP2 in the dilated state half map 2

Fileemd_41847_half_map_2.map
AnnotationTRPV1 bound with diC8-PIP2 in the dilated state half map 2
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state

EntireName: TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state
Components
  • Complex: TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state
    • Protein or peptide: Transient receptor potential cation channel subfamily V member 1
  • Ligand: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate
  • Ligand: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE
  • Ligand: CHOLESTEROL
  • Ligand: SODIUM ION
  • Ligand: water

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Supramolecule #1: TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state

SupramoleculeName: TRPV1 in nanodisc bound with diC8-PIP2 in the dilated state
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 688 KDa

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Macromolecule #1: Transient receptor potential cation channel subfamily V member 1

MacromoleculeName: Transient receptor potential cation channel subfamily V member 1
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 72.888227 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: 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

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Macromolecule #2: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(o...

MacromoleculeName: [(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate
type: ligand / ID: 2 / Number of copies: 4 / Formula: PIO
Molecular weightTheoretical: 746.566 Da
Chemical component information

ChemComp-PIO:
[(2R)-2-octanoyloxy-3-[oxidanyl-[(1R,2R,3S,4R,5R,6S)-2,3,6-tris(oxidanyl)-4,5-diphosphonooxy-cyclohexyl]oxy-phosphoryl]oxy-propyl] octanoate

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Macromolecule #3: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE

MacromoleculeName: 1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / type: ligand / ID: 3 / Number of copies: 4 / Formula: PCW
Molecular weightTheoretical: 787.121 Da
Chemical component information

ChemComp-PCW:
1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE / DOPC, phospholipid*YM

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Macromolecule #4: CHOLESTEROL

MacromoleculeName: CHOLESTEROL / type: ligand / ID: 4 / Number of copies: 4 / Formula: CLR
Molecular weightTheoretical: 386.654 Da
Chemical component information

ChemComp-CLR:
CHOLESTEROL

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Macromolecule #5: SODIUM ION

MacromoleculeName: SODIUM ION / type: ligand / ID: 5 / Number of copies: 1
Molecular weightTheoretical: 22.99 Da

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Macromolecule #6: water

MacromoleculeName: water / type: ligand / ID: 6 / Number of copies: 24 / Formula: HOH
Molecular weightTheoretical: 18.015 Da
Chemical component information

ChemComp-HOH:
WATER

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

Concentration2.1 mg/mL
BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 45.8 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination 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

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Image processing

Startup modelType of model: EMDB MAP
EMDB ID:

8118

Final reconstructionApplied symmetry - Point group: C4 (4 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.6 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 26265
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION
FSC plot (resolution estimation)

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