9UED
Cryo-EM structure of human TRPV3 in complex with sevoflurane determined in MSP2N2 nanodisc
This is a non-PDB format compatible entry.
Summary for 9UED
| Entry DOI | 10.2210/pdb9ued/pdb |
| EMDB information | 64082 |
| Descriptor | Transient receptor potential cation channel subfamily V member 3, sevoflurane, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate (3 entities in total) |
| Functional Keywords | transient receptor potential vanilloid 3, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 374721.42 |
| Authors | |
| Primary citation | Wang, P.,Zhu, J.,Lu, X.,Chen, C.,Gao, B.,Tao, W.,Xia, K.,Song, Y.,Shi, Q.,Gai, H.,Xiao, P.,Liu, F.,Pang, P.,Li, Y.,Mo, X.,Wang, X.D.,Xie, C.,Li, D.,Zhang, Z.,Yao, J. Vagal nerve TRPV3 regulates sedative-mediated appeasement. Proc.Natl.Acad.Sci.USA, 123:e2525757123-e2525757123, 2026 Cited by PubMed 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, 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. PubMed: 41989856DOI: 10.1073/pnas.2525757123 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.29 Å) |
Structure validation
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