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- EMDB-64082: Cryo-EM structure of human TRPV3 in complex with sevoflurane dete... -

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Basic information

Entry
Database: EMDB / ID: EMD-64082
TitleCryo-EM structure of human TRPV3 in complex with sevoflurane determined in MSP2N2 nanodisc
Map data
Sample
  • Complex: Transient Receptor Potential Vanilloid 3 in complex with sevoflurane
    • Protein or peptide: Transient receptor potential cation channel subfamily V member 3
  • Ligand: sevoflurane
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
KeywordsTransient Receptor Potential Vanilloid 3 / MEMBRANE PROTEIN
Function / homology
Function and homology information


negative regulation of hair cycle / osmosensory signaling pathway / response to temperature stimulus / TRP channels / positive regulation of calcium ion import / sodium channel activity / calcium ion import across plasma membrane / actin filament organization / calcium ion transmembrane transport / calcium channel activity ...negative regulation of hair cycle / osmosensory signaling pathway / response to temperature stimulus / TRP channels / positive regulation of calcium ion import / sodium channel activity / calcium ion import across plasma membrane / actin filament organization / calcium ion transmembrane transport / calcium channel activity / lysosome / signaling receptor complex / cilium / metal ion binding / identical protein binding / plasma membrane / cytoplasm
Similarity search - Function
Transient receptor potential cation channel subfamily V member 1-4 / Transient receptor potential cation channel subfamily V / Ankyrin repeat / Ankyrin repeat profile. / Ankyrin repeats (3 copies) / 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 3
Similarity search - Component
Biological speciesHomo sapiens (human)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.29 Å
AuthorsLu X / Yao J
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32371200 China
CitationJournal: Proc Natl Acad Sci U S A / Year: 2026
Title: Vagal nerve TRPV3 regulates sedative-mediated appeasement.
Authors: Peiyu Wang / Jinpiao Zhu / Xuteng Lu / Chang Chen / Bomin Gao / Wanjiang Tao / Keyu Xia / Yang Song / Qiong Shi / Hongcun Gai / Panhao Xiao / Feng Liu / Peiyuan Pang / Yang Li / Xiaoyi Mo / ...Authors: Peiyu Wang / Jinpiao Zhu / Xuteng Lu / Chang Chen / Bomin Gao / Wanjiang Tao / Keyu Xia / Yang Song / Qiong Shi / Hongcun Gai / Panhao Xiao / Feng Liu / Peiyuan Pang / Yang Li / Xiaoyi Mo / Xiao-Dong Wang / Chang Xie / Dongdong Li / Zongze Zhang / Jing Yao /
Abstract: Aromatic essential oils (EOs) exhibit anxiolytic properties, yet their neural and molecular mechanisms remain to be understood. Here, we found that citronellal, an EO derived from lemongrass, ...Aromatic essential oils (EOs) exhibit anxiolytic properties, yet their neural and molecular mechanisms remain to be understood. Here, we found that citronellal, an EO derived from lemongrass, alleviates stress-related anxiety by modulating vagal tone. We identified transient receptor potential vanilloid 3 (TRPV3) channel in nodose ganglion (NG) as the molecular target of citronellal. TRPV3 was also observed to mediate the antistress effects of the inhaled anesthetic sevoflurane. Both sedatives attenuated acute restraint stress-induced hyperactivity of heart and breath rates via glutamatergic neurotransmission along NG-to-caudal nucleus tractus solitarius (cNTS) pathway. This effect was abolished by surgical vagotomy, , or NG-specific knockdown. Cryo-EM structural analysis revealed that sevoflurane occupies a pore-proximal fenestration site, while citronellal binds to the vanilloid site. Re-expression of wild-type TRPV3, but not loss-of-function TRPV3 mutants TRPV3(A560L) or TRPV3(V662A), in NG neurons restored the mouse's response to both sedatives, thereby modulating heart and respiratory rates. Together, these findings establish peripheral TRPV3 as a multisensory ligand-gated node for vagal modulation of stress responses, and help instruct pathway-specific anxiolytics.
History
DepositionApr 8, 2025-
Header (metadata) releaseApr 8, 2026-
Map releaseApr 8, 2026-
UpdateJun 10, 2026-
Current statusJun 10, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_64082.png

Downloads & links

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Map

FileDownload / File: emd_64082.map.gz / Format: CCP4 / Size: 125 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
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Others
AxesZ (Sec.)Y (Row.)X (Col.)
1.07 Å/pix.
x 320 pix.
= 342.4 Å		1.07 Å/pix.
x 320 pix.
= 342.4 Å		1.07 Å/pix.
x 320 pix.
= 342.4 Å

Surface

Projections

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Images are generated by Spider.

Voxel sizeX=Y=Z: 1.07 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.2
Minimum - Maximum-1.0435643 - 2.0869992
Average (Standard dev.)-0.00048775057 (±0.0433464)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions320320320
Spacing320320320
CellA=B=C: 342.40002 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #1

Fileemd_64082_half_map_1.map
Projections & Slices
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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #2

Fileemd_64082_half_map_2.map
Projections & Slices
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Sample components

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Entire : Transient Receptor Potential Vanilloid 3 in complex with sevoflurane

EntireName: Transient Receptor Potential Vanilloid 3 in complex with sevoflurane
Components
  • Complex: Transient Receptor Potential Vanilloid 3 in complex with sevoflurane
    • Protein or peptide: Transient receptor potential cation channel subfamily V member 3
  • Ligand: sevoflurane
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate

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Supramolecule #1: Transient Receptor Potential Vanilloid 3 in complex with sevoflurane

SupramoleculeName: Transient Receptor Potential Vanilloid 3 in complex with sevoflurane
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Homo sapiens (human)

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Macromolecule #1: Transient receptor potential cation channel subfamily V member 3

MacromoleculeName: Transient receptor potential cation channel subfamily V member 3
type: protein_or_peptide / ID: 1 / Number of copies: 4 / Enantiomer: LEVO
Source (natural)Organism: Homo sapiens (human)
Molecular weightTheoretical: 91.960148 KDa
Recombinant expressionOrganism: Komagataella pastoris (fungus)
SequenceString: MKAHPKEMVP LMGKRVAAPS GNPAVLPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS PPVFSKPMDS NIRQCISGNC DDMDSPQSP QDDVTETPSN PNSPSAQLAK EEQRRKKRRL KKRIFAAVSE GCVEELVELL VELQELCRRR HDEDVPDFLM H KLTASDTG ...String:
MKAHPKEMVP LMGKRVAAPS GNPAVLPEKR PAEITPTKKS AHFFLEIEGF EPNPTVAKTS PPVFSKPMDS NIRQCISGNC DDMDSPQSP QDDVTETPSN PNSPSAQLAK EEQRRKKRRL KKRIFAAVSE GCVEELVELL VELQELCRRR HDEDVPDFLM H KLTASDTG KTCLMKALLN INPNTKEIVR ILLAFAEEND ILGRFINAEY TEEAYEGQTA LNIAIERRQG DIAALLIAAG AD VNAHAKG AFFNPKYQHE GFYFGETPLA LAACTNQPEI VQLLMEHEQT DITSRDSRGN NILHALVTVA EDFKTQNDFV KRM YDMILL RSGNWELETT RNNDGLTPLQ LAAKMGKAEI LKYILSREIK EKRLRSLSRK FTDWAYGPVS SSLYDLTNVD TTTD NSVLE ITVYNTNIDN RHEMLTLEPL HTLLHMKWKK FAKHMFFLSF CFYFFYNITL TLVSYYRPRE EEAIPHPLAL THKMG WLQL LGRMFVLIWA MCISVKEGIA IFLLRPSDLQ SILSDAWFHF VFFIQAVLVI LSVFLYLFAY KEYLACLVLA MALGWA NML YYTRGFQSMG MYSVMIQKVI LHDVLKFLFV YIVFLLGFGV ALASLIEKCP KDNKDCSSYG SFSDAVLELF KLTIGLG DL NIQQNSKYPI LFLFLLITYV ILTFVLLLNM LIALMGETVE NVSKESERIW RLQRARTILE FEKMLPEWLR SRFRMGEL C KVAEDDFRLC LRINEVKWTE WKTHVSFLNE DPGPVRRTDF NKIQDSSRNN SKTTLNAFEE VEEFPETSVA AASNSLEVL FQ

UniProtKB: Transient receptor potential cation channel subfamily V member 3

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Macromolecule #2: sevoflurane

MacromoleculeName: sevoflurane / type: ligand / ID: 2 / Number of copies: 4 / Formula: A1IPI
Molecular weightTheoretical: 200.055 Da

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Macromolecule #3: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 3 / Number of copies: 8 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

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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

BufferpH: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS KRIOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: -1.5 µm / Nominal defocus min: -1.3 µm
Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company

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Image processing

CTF correctionType: NONE
Startup modelType of model: PDB ENTRY
PDB model - PDB ID:

9jee

Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 38843
Initial angle assignmentType: ANGULAR RECONSTITUTION
Final angle assignmentType: ANGULAR RECONSTITUTION

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