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. 2025 Jan 2;33(1):91-103.e5.
doi: 10.1016/j.str.2024.10.018. Epub 2024 Nov 4.

Structure-function analyses of human TRPV6 ancestral and derived haplotypes

Arthur Neuberger  1 , Alexey Shalygin  2 , Yury A Trofimov  3 , Irina I Veretenenko  3 , Kirill D Nadezhdin  1 , Nikolay A Krylov  3 , Thomas Gudermann  4 , Roman G Efremov  5 , Vladimir Chubanov  2 , Alexander I Sobolevsky  6
Affiliations

Structure-function analyses of human TRPV6 ancestral and derived haplotypes

Arthur Neuberger et al. Structure. .

Abstract

TRPV6 is a Ca2+ selective channel that mediates calcium uptake in the gut and contributes to the development and progression of human cancers. TRPV6 is represented by the ancestral and derived haplotypes that differ by three non-synonymous polymorphisms, located in the N-terminal ankyrin repeat domain (C157R), S1-S2 extracellular loop (M378V), and C-terminus (M681T). The ancestral and derived haplotypes were proposed to serve as genomic factors causing a different outcome for cancer patients of African ancestry. We solved cryoelectron microscopy (cryo-EM) structures of ancestral and derived TRPV6 in the open and calmodulin (CaM)-bound inactivated states. Neither state shows substantial structural differences caused by the non-synonymous polymorphisms. Functional properties assessed by electrophysiological recordings and Ca2+ uptake measurements, and water and ion permeation evaluated by molecular modeling also appear similar between the haplotypes. Therefore, ancestral and derived TRPV6 have similar structure and function, implying that other factors are responsible for the differences in susceptibility to cancer.

Keywords: TRP channels; TRPV6; ancestral; cancer; cryo-EM; derived; dynamic molecular portraits of TRPV6 pore domain; oncochannel.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

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References

    1. Fecher-Trost C, Weissgerber P & Wissenbach U TRPV6 channels. (2014) Mammalian Transient Receptor Potential (TRP) Cation Channels, 359–384, doi: 10.1007/978-3-642-54215-2_14. - DOI - PubMed
    1. Khattar V, Wang L & Peng J-B Calcium Selective Channel TRPV6: Structure, Function, and Implications in Health and Disease. (2022) Gene, 146192, doi: 10.1016/j.gene.2022.146192. - DOI - PMC - PubMed
    1. Yelshanskaya MV, Nadezhdin KD, Kurnikova MG & Sobolevsky AI (2021) Structure and function of the calcium-selective TRP channel TRPV6. The Journal of physiology 599, 2673–2697, doi: 10.1113/JP279024. - DOI - PMC - PubMed
    1. Neuberger A & Sobolevsky AI (2023) Molecular pharmacology of the onco-TRP channel TRPV6. Channels (Austin) 17, 2266669, doi:10.1080/19336950.2023.2266669. - DOI - PMC - PubMed
    1. Nett V, Erhardt N, Wyatt A & Wissenbach U (2021) Human TRPV6-pathies caused by gene mutations. Biochimica et Biophysica Acta (BBA)-General Subjects 1865, 129873, doi: 10.1016/j.bbagen.2021.129873. - DOI - PubMed

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