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The human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain

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    SYSNO ASEP0563535
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleThe human TRPA1 intrinsic cold and heat sensitivity involves separate channel structures beyond the N-ARD domain
    Author(s) Moparthi, L. (SE)
    Sinica, Viktor (FGU-C) RID, ORCID, SAI
    Moparthi, V. K. (SE)
    Kreir, M. (BE)
    Vignane, T. (DE)
    Filipovic, M. R. (DE)
    Vlachová, Viktorie (FGU-C) RID, ORCID, SAI
    Zygmunt, P. M. (SE)
    Article number6113
    Source TitleNature Communications. - : Nature Publishing Group
    Roč. 13, č. 1 (2022)
    Number of pages15 s.
    Languageeng - English
    CountryGB - United Kingdom
    KeywordsTRP channel ; structure-function ; thermoTRP
    OECD categoryNeurosciences (including psychophysiology
    R&D ProjectsGA22-13750S GA ČR - Czech Science Foundation (CSF)
    Method of publishingOpen access
    Institutional supportFGU-C - RVO:67985823
    UT WOS000871026900011
    EID SCOPUS85139943046
    DOI10.1038/s41467-022-33876-8
    AnnotationTRP channels sense temperatures ranging from noxious cold to noxious heat. Whether specialized TRP thermosensor modules exist and how they control channel pore gating is unknown. We studied purified human TRPA1 (hTRPA1) truncated proteins to gain insight into the temperature gating of hTRPA1. In patch-clamp bilayer recordings, Delta 1-688 hTRPA1, without the N-terminal ankyrin repeat domain (N-ARD), was more sensitive to cold and heat, whereas Delta 1-854 hTRPA1, also lacking the S1-S4 voltage sensing-like domain (VSLD), gained sensitivity to cold but lost its heat sensitivity. In hTRPA1 intrinsic tryptophan fluorescence studies, cold and heat evoked rearrangement of VSLD and the C-terminus domain distal to the transmembrane pore domain S5-S6 (CTD). In whole-cell electrophysiology experiments, replacement of the CTD located cysteines 1021 and 1025 with alanine modulated hTRPA1 cold responses. It is proposed that hTRPA1 CTD harbors cold and heat sensitive domains allosterically coupled to the S5-S6 pore region and the VSLD, respectively.
    WorkplaceInstitute of Physiology
    ContactLucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
    Year of Publishing2023
    Electronic addresshttps://doi.org/10.1038/s41467-022-33876-8
Number of the records: 1  

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