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- PDB-9ued: Cryo-EM structure of human TRPV3 in complex with sevoflurane dete... -

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Basic information

Entry
Database: PDB / ID: 9ued
TitleCryo-EM structure of human TRPV3 in complex with sevoflurane determined in MSP2N2 nanodisc
ComponentsTransient receptor potential cation channel subfamily V member 3
KeywordsMEMBRANE PROTEIN / Transient Receptor Potential Vanilloid 3
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
: / Chem-POV / Transient receptor potential cation channel subfamily V member 3
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.29 Å
AuthorsLu, X. / Yao, J.
Funding support China, 1items
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, 2025Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Apr 8, 2026Provider: repository / Type: Initial release
Revision 1.0Apr 8, 2026Data content type: EM metadata / Data content type: EM metadata / Provider: repository / Type: Initial release
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Revision 1.0Apr 8, 2026Data content type: Primary map / Data content type: Primary map / Provider: repository / Type: Initial release
Revision 1.1Jun 10, 2026Group: Data collection / Database references / Category: citation / citation_author / em_admin
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Revision 1.1Jun 10, 2026Data content type: EM metadata / Data content type: EM metadata / EM metadata / Group: Database references / Experimental summary / Data content type: EM metadata / EM metadata / EM metadata / Category: citation / citation_author / em_admin
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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

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Assembly

Deposited unit
A: Transient receptor potential cation channel subfamily V member 3
B: Transient receptor potential cation channel subfamily V member 3
C: Transient receptor potential cation channel subfamily V member 3
D: Transient receptor potential cation channel subfamily V member 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)374,72116
Polymers367,8414
Non-polymers6,88112
Water00
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: electron microscopy, not applicable
TypeNameSymmetry operationNumber
identity operation1_5551

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Components

#1: Protein
Transient receptor potential cation channel subfamily V member 3 / TrpV3 / Vanilloid receptor-like 3 / VRL-3


Mass: 91960.148 Da / Num. of mol.: 4
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: TRPV3 / Production host: Komagataella pastoris (fungus) / References: UniProt: Q8NET8
#2: Chemical
ChemComp-A1IPI / sevoflurane / 1,1,1,3,3,3-hexakis(fluoranyl)-2-(fluoranylmethoxy)propane / sevorane


Mass: 200.055 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C4H3F7O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-POV / (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / POPC


Mass: 760.076 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C42H82NO8P / Comment: phospholipid*YM
Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

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Sample preparation

ComponentName: Transient Receptor Potential Vanilloid 3 in complex with sevoflurane
Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Komagataella pastoris (fungus)
Buffer solutionpH: 7.4
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
VitrificationCryogen name: ETHANE

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Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: TFS KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELD / Nominal defocus max: -1500 nm / Nominal defocus min: -1300 nm
Image recordingElectron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

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Processing

EM softwareName: PHENIX / Version: 1.20.1_4487 / Category: model refinement
CTF correctionType: NONE
3D reconstructionResolution: 3.29 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 38843 / Symmetry type: POINT
RefinementHighest resolution: 3.29 Å
Stereochemistry target values: REAL-SPACE (WEIGHTED MAP SUM AT ATOM CENTERS)
Refine LS restraints
Refine-IDTypeDev idealNumber
ELECTRON MICROSCOPYf_bond_d0.00320428
ELECTRON MICROSCOPYf_angle_d0.4827556
ELECTRON MICROSCOPYf_dihedral_angle_d10.3382896
ELECTRON MICROSCOPYf_chiral_restr0.0333112
ELECTRON MICROSCOPYf_plane_restr0.0033368

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