9PJ6

Inactivated-state structure of wild-type human TRPV3 purified in GDN detergent

Summary for 9PJ6

• Entry DOI: 10.2210/pdb9pj6/pdb
• EMDB information: 71681
• Descriptor: Transient receptor potential cation channel subfamily V member 3, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, SODIUM ION, ... (4 entities in total)
• Functional Keywords: trpv3, wild type, human, inactivated state, gdn, detergent, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 4
• Total formula weight: 395134.46

Authors

Purohit, R.,Khau, J.,Nadezhdin, K.D.,Sobolevsky, A.I. (deposition date: 2025-07-11, release date: 2026-07-01)

Primary citation

Khau, J.,Purohit, R.,Nadezhdin, K.D.,Talyzina, I.A.,Sobolevsky, A.I.
Structural diversity of heat-sensing channel TRPV3 with Olmsted syndrome mutations.
Nat Commun, 2026

PubMed Abstract: Mutations in TRPV3, a temperature-sensitive ion channel critical for skin physiology, cause severe genodermatosis called Olmsted syndrome (OS). Here we integrate single-channel recordings and cryo-EM to characterize five OS mutants. All exhibit reduced temperature sensitivity in the temperature range relevant to normal skin physiology and disrupt structural elements stabilizing non-conducting states, including vanilloid lipid coordination and S4-S5 linker-TRP helix contacts. Despite shared gain-of-function phenotype, the mutations cause different distributions of the TRPV3 closed, open, and inactivated states. One mutation expands the conformational ensemble with noncanonical two-fold-symmetrical states featuring dramatic domain swapping. Our findings highlight conserved TRP channel gating mechanisms and suggest that OS mutations alter TRPV3 function by triggering the conformational wave that mediates gating in wild-type channels. These insights establish a framework to decode genotype-structure-function relationships in TRP channelopathies and guide future therapeutic strategies.

PubMed: 42323291
DOI: 10.1038/s41467-026-74687-5

Experimental method

ELECTRON MICROSCOPY (2.97 Å)