dc.creatorFlores-Aldama, Lisandra
dc.creatorBustos, Daniel
dc.creatorCabezas-Bratesco, Deny
dc.creatorGonzalez, Wendy
dc.creatorBrauchi, Sebastian E
dc.date2023-03-29T12:39:11Z
dc.date2023-03-29T12:39:11Z
dc.date2023
dc.date.accessioned2024-05-02T20:30:51Z
dc.date.available2024-05-02T20:30:51Z
dc.identifierhttp://repositorio.ucm.cl/handle/ucm/4599
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/9274839
dc.descriptionTRPV5 and TRPV6 are calcium-selective ion channels expressed at the apical membrane of epithelial cells. Important for systemic calcium (Ca2+) homeostasis, these channels are considered gatekeepers of this cation transcellular transport. Intracellular Ca2+ exerts a negative control over the activity of these channels by promoting inactivation. TRPV5 and TRPV6 inactivation has been divided into fast and slow phases based on their kinetics. While slow inactivation is common to both channels, fast inactivation is characteristic of TRPV6. It has been proposed that the fast phase depends on Ca2+ binding and that the slow phase depends on the binding of the Ca2+/Calmodulin complex to the internal gate of the channels. Here, by means of structural analyses, site-directed mutagenesis, electrophysiology, and molecular dynamic simulations, we identified a specific set of amino acids and interactions that determine the inactivation kinetics of mammalian TRPV5 and TRPV6 channels. We propose that the association between the intracellular helix-loop-helix (HLH) domain and the TRP domain helix (TDh) favors the faster inactivation kinetics observed in mammalian TRPV6 channels.
dc.languageen
dc.rightsAtribución-NoComercial-SinDerivadas 3.0 Chile
dc.rightshttp://creativecommons.org/licenses/by-nc-nd/3.0/cl/
dc.sourceInternational Journal of Molecular Sciences, 24(5), 4470
dc.subjectTRP channels
dc.subjectInactivation
dc.subjectTRPV5
dc.subjectTRPV6
dc.subjectMolecular evolution
dc.titleIntracellular Helix-Loop-Helix domain modulates inactivation kinetics of mammalian TRPV5 and TRPV6 channels
dc.typeArticle


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