13LR

Structure of human TRPV3-G568D Olmsted syndrome mutant in the 4-fold symmetrical inactivated state

13LR の概要

• エントリーDOI: 10.2210/pdb13lr/pdb
• EMDBエントリー: 77142
• 分子名称: Isoform 2 of Transient receptor potential cation channel subfamily V member 3,Green fluorescent protein, (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate, SODIUM ION (3 entities in total)
• 機能のキーワード: trpv3, olmsted syndrome, g568d, mutation, gain-of-function, inactivated state, c4 symmetry, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 489973.85

構造登録者

Nadezhdin, K.D.,Khau, J.,Purohit, R.,Sobolevsky, A.I. (登録日: 2026-05-13, 公開日: 2026-07-01)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.33 Å)