13lu

Structure of human TRPV3-W521S Olmsted syndrome mutant in the closed state

spinqualitylabelsall models 13lu, resolution 2.49Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 13lu is a 4 chain structure with sequence from Aequorea victoria and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 2.49Å Ligands: NA, POV Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease TRPV3_HUMAN Mutilating palmoplantar keratoderma with periorificial keratotic plaques. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Function TRPV3_HUMAN Putative receptor-activated non-selective calcium permeant cation channel. It is activated by innocuous (warm) temperatures and shows an increased response at noxious temperatures greater than 39 degrees Celsius. Activation exhibits an outward rectification. May associate with TRPV1 and may modulate its activity. Is a negative regulator of hair growth and cycling: TRPV3-coupled signaling suppresses keratinocyte proliferation in hair follicles and induces apoptosis and premature hair follicle regression (catagen). GFP_AEQVI Energy-transfer acceptor. Its role is to transduce the blue chemiluminescence of the protein aequorin into green fluorescent light by energy transfer. Fluoresces in vivo upon receiving energy from the Ca(2+)-activated photoprotein aequorin. Publication Abstract from PubMed 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. Structural diversity of heat-sensing channel TRPV3 with Olmsted syndrome mutations.,Khau J, Purohit R, Nadezhdin KD, Talyzina IA, Sobolevsky AI Nat Commun. 2026 Jun 20. doi: 10.1038/s41467-026-74687-5. PMID:42323291 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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