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- EMDB-14748: TRPV2-C16+Pro-2 -

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ID or keywords:

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Basic information

Entry
Database: EMDB / ID: EMD-14748
TitleTRPV2-C16+Pro-2
Map data
Sample
  • Complex: TRPV2-C16+Pro-2
    • Protein or peptide: Transient receptor potential cation channel subfamily V member 2
KeywordsTemperature sensor / MEMBRANE PROTEIN
Function / homology
Function and homology information


growth cone membrane / response to temperature stimulus / positive regulation of calcium ion import / positive regulation of axon extension / axonal growth cone / calcium channel activity / positive regulation of cold-induced thermogenesis / cell body / cell surface
Similarity search - Function
Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / 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 2
Similarity search - Component
Biological speciesRattus norvegicus (Norway rat)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.39 Å
AuthorsZhang L / Gourdon P / Zygmunt PM
Funding support1 items
OrganizationGrant numberCountry
Not funded
CitationJournal: Nat Commun / Year: 2022
Title: Cannabinoid non-cannabidiol site modulation of TRPV2 structure and function.
Authors: Liying Zhang / Charlotte Simonsen / Lucie Zimova / Kaituo Wang / Lavanya Moparthi / Rachelle Gaudet / Maria Ekoff / Gunnar Nilsson / Ute A Hellmich / Viktorie Vlachova / Pontus Gourdon / Peter M Zygmunt /
Abstract: TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore ...TRPV2 is a ligand-operated temperature sensor with poorly defined pharmacology. Here, we combine calcium imaging and patch-clamp electrophysiology with cryo-electron microscopy (cryo-EM) to explore how TRPV2 activity is modulated by the phytocannabinoid Δ-tetrahydrocannabiorcol (C16) and by probenecid. C16 and probenecid act in concert to stimulate TRPV2 responses including histamine release from rat and human mast cells. Each ligand causes distinct conformational changes in TRPV2 as revealed by cryo-EM. Although the binding for probenecid remains elusive, C16 associates within the vanilloid pocket. As such, the C16 binding location is distinct from that of cannabidiol, partially overlapping with the binding site of the TRPV2 inhibitor piperlongumine. Taken together, we discover a new cannabinoid binding site in TRPV2 that is under the influence of allosteric control by probenecid. This molecular insight into ligand modulation enhances our understanding of TRPV2 in normal and pathophysiology.
History
DepositionApr 11, 2022-
Header (metadata) releaseJan 18, 2023-
Map releaseJan 18, 2023-
UpdateJul 24, 2024-
Current statusJul 24, 2024Processing site: PDBe / Status: Released

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Structure visualization

Supplemental images

Downloads & links

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Map

FileDownload / File: emd_14748.map.gz / Format: CCP4 / Size: 178 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.85 Å/pix.
x 360 pix.
= 304.704 Å
0.85 Å/pix.
x 360 pix.
= 304.704 Å
0.85 Å/pix.
x 360 pix.
= 304.704 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.8464 Å
Density
Contour LevelBy AUTHOR: 0.3
Minimum - Maximum-1.5356241 - 2.7874916
Average (Standard dev.)0.00027602367 (±0.054068565)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions360360360
Spacing360360360
CellA=B=C: 304.704 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_14748_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Half map: #1

Fileemd_14748_half_map_2.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

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Sample components

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Entire : TRPV2-C16+Pro-2

EntireName: TRPV2-C16+Pro-2
Components
  • Complex: TRPV2-C16+Pro-2
    • Protein or peptide: Transient receptor potential cation channel subfamily V member 2

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Supramolecule #1: TRPV2-C16+Pro-2

SupramoleculeName: TRPV2-C16+Pro-2 / type: complex / ID: 1 / Parent: 0 / Macromolecule list: all
Source (natural)Organism: Rattus norvegicus (Norway rat)

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Macromolecule #1: Transient receptor potential cation channel subfamily V member 2

MacromoleculeName: Transient receptor potential cation channel subfamily V member 2
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Rattus norvegicus (Norway rat)
Molecular weightTheoretical: 116.426359 KDa
Recombinant expressionOrganism: Saccharomyces cerevisiae (brewer's yeast)
SequenceString: MTSASSPPAF RLETSDGDEE GNAEVNKGKQ EPPPMESPFQ REDRNSSPQI KVNLNFIKRP PKNTSAPSQQ EPDRFDRDRL FSVVSRGVP EELTGLLEYL RWNSKYLTDS AYTEGSTGKT CLMKAVLNLQ DGVNACIMPL LQIDKDSGNP KPLVNAQCID E FYQGHSAL ...String:
MTSASSPPAF RLETSDGDEE GNAEVNKGKQ EPPPMESPFQ REDRNSSPQI KVNLNFIKRP PKNTSAPSQQ EPDRFDRDRL FSVVSRGVP EELTGLLEYL RWNSKYLTDS AYTEGSTGKT CLMKAVLNLQ DGVNACIMPL LQIDKDSGNP KPLVNAQCID E FYQGHSAL HIAIEKRSLQ CVKLLVENGA DVHLRACGRF FQKHQGTCFY FGELPLSLAA CTKQWDVVTY LLENPHQPAS LE ATDSLGN TVLHALVMIA DNSPENSALV IHMYDGLLQM GARLCPTVQL EEISNHQGLT PLKLAAKEGK IEIFRHILQR EFS GPYQPL SRKFTEWCYG PVRVSLYDLS SVDSWEKNSV LEIIAFHCKS PNRHRMVVLE PLNKLLQEKW DRLVSRFFFN FACY LVYMF IFTVVAYHQP SLDQPAIPSS KATFGESMLL LGHILILLGG IYLLLGQLWY FWRRRLFIWI SFMDSYFEIL FLLQA LLTV LSQVLRFMET EWYLPLLVLS LVLGWLNLLY YTRGFQHTGI YSVMIQKVIL RDLLRFLLVY LVFLFGFAVA LVSLSR EAR SPKAPEDSSS TVTEQPTVGQ EEEPAPYRSI LDASLELFKF TIGMGELAFQ EQLRFRGVVL LLLLAYVLLT YVLLLNM LI ALMSETVNHV ADNSWSIWKL QKAISVLEME NGYWWCRRKK HREGRLLKVG TRGDGTPDER WCFRVEEVNW AAWEKTLP T LSEDPSGPGI TGNKKNPTSK PGKNSASEED HLPLQVLQSP AAAGLVPRGS VAAAVSKGEE LFTGVVPILV ELDGDVNGH KFSVSGEGEG DATYGKLTLK FICTTGKLPV PWPTLVTTLT YGVQCFSRYP DHMKQHDFFK SAMPEGYVQE RTIFFKDDGN YKTRAEVKF EGDTLVNRIE LKGIDFKEDG NILGHKLEYN YNSHNVYIMA DKQKNGIKVN FKIRHNIEDG SVQLADHYQQ N TPIGDGPV LLPDNHYLST QSKLSKDPNE KRDHMVLLEF VTAAGITLGM DELYKSGLRS HHHHHHHH

UniProtKB: Transient receptor potential cation channel, subfamily V, member 2

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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

Concentration0.4 mg/mL
BufferpH: 8
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TITAN KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 48.4 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.7 µm / Nominal defocus min: 0.7000000000000001 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

Startup modelType of model: NONE
Final reconstructionApplied symmetry - Point group: C1 (asymmetric) / Resolution.type: BY AUTHOR / Resolution: 3.39 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 326000
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD

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