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TitlePlant essential oil targets TRPV3 for skin renewal and structural mechanism of action.
Journal, issue, pagesNat Commun, Vol. 16, Issue 1, Page 2728, Year 2025
Publish dateMar 19, 2025
AuthorsYang Li / Xuteng Lu / Xufeng Cheng / Keyu Xia / Junyan Hu / Peiyu Wang / Peiyuan Pang / Bomin Gao / Demeng Sun / Zhuzhen Zhang / Dongdong Li / Zengqin Deng / Changlin Tian / Chang Xie / Jing Yao /
PubMed AbstractOur skin safeguards the body homeostasis for health and also provides psychological consolation in social life. Natural essential oils are widely used for skin maintenance, while the molecular target ...Our skin safeguards the body homeostasis for health and also provides psychological consolation in social life. Natural essential oils are widely used for skin maintenance, while the molecular target and mechanism of action remain largely unknown. Here, we report that citronellal, a plant-derived acyclic monoterpene commonly used for personal care, stimulates skin renewal by promoting keratinocyte proliferation through the activation of TRPV3. We further present cryo-EM structures of human TRPV3 in complex with acyclic monoterpenes, including citronellal, citral, linalool and isodihydrolavandulal, determined at resolutions of 3.1-3.6 Å. Our structural and functional analysis unmasks consistent yet subtly different binding modes within the TRPV3 vanilloid site. Our results elucidate that essential oil ligands activate TRPV3 channels by competitively displacing endogenous lipids from the vanilloid site. Together, these findings identify TRPV3 as the molecular target of natural acyclic monoterpenes for skin renewal, and delineate the structural basis of action, thus being instrumental for moving forward skin healthcare.
External linksNat Commun / PubMed:40108208 / PubMed Central
MethodsEM (single particle)
Resolution3.13 - 3.62 Å
Structure data

61396

9jdm

EMDB-61396, PDB-9jdm:
Cryo-EM structure of human TRPV3 determined in MSP2N2 nanodisc
Method: EM (single particle) / Resolution: 3.13 Å

61407

9je5

EMDB-61407, PDB-9je5:
Cryo-EM structure of human TRPV3 in complex with citronellal determined in MSP2N2 nanodisc
Method: EM (single particle) / Resolution: 3.53 Å

61414

9jee

EMDB-61414, PDB-9jee:
Cryo-EM structure of human TRPV3 in complex with citral determined in MSP2N2 nanodisc
Method: EM (single particle) / Resolution: 3.51 Å

61415

9jef

EMDB-61415, PDB-9jef:
Cryo-EM structure of human TRPV3 in complex with linalool determined in MSP2N2 nanodisc
Method: EM (single particle) / Resolution: 3.62 Å

61416

9jeg

EMDB-61416, PDB-9jeg:
Cryo-EM structure of human TRPV3 in complex with isodihydrolavandulal determined in MSP2N2 nanodisc
Method: EM (single particle) / Resolution: 3.39 Å

Chemicals

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

PDB-1ebv:
OVINE PGHS-1 COMPLEXED WITH SALICYL HYDROXAMIC ACID

ChemComp-GRQ:
Geranaldehyde

PDB-1ebl:
THE 1.8 A CRYSTAL STRUCTURE AND ACTIVE SITE ARCHITECTURE OF BETA-KETOACYL-[ACYL CARRIER PROTEIN] SYNTHASE III (FABH) FROM ESCHERICHIA COLI

PDB-1ebm:
CRYSTAL STRUCTURE OF THE HUMAN 8-OXOGUANINE GLYCOSYLASE (HOGG1) BOUND TO A SUBSTRATE OLIGONUCLEOTIDE

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN

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