6mhs
From Proteopedia
Structure of the human TRPV3 channel in a putative sensitized conformation
Structural highlights
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).[1] [2] [3] Publication Abstract from PubMedTransient receptor potential vanilloid channel 3 (TRPV3), a member of the thermosensitive TRP (thermoTRPV) channels, is activated by warm temperatures and serves as a key regulator of normal skin physiology through the release of pro-inflammatory messengers. Mutations in trpv3 have been identified as the cause of the congenital skin disorder, Olmsted syndrome. Unlike other members of the thermoTRPV channel family, TRPV3 sensitizes upon repeated stimulation, yet a lack of structural information about the channel precludes a molecular-level understanding of TRPV3 sensitization and gating. Here, we present the cryo-electron microscopy structures of apo and sensitized human TRPV3, as well as several structures of TRPV3 in the presence of the common thermoTRPV agonist 2-aminoethoxydiphenyl borate (2-APB). Our results show alpha-to-pi-helix transitions in the S6 during sensitization, and suggest a critical role for the S4-S5 linker pi-helix during ligand-dependent gating. Conformational ensemble of the human TRPV3 ion channel.,Zubcevic L, Herzik MA Jr, Wu M, Borschel WF, Hirschi M, Song AS, Lander GC, Lee SY Nat Commun. 2018 Nov 14;9(1):4773. doi: 10.1038/s41467-018-07117-w. PMID:30429472[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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