Trace amine associated receptors (TAARs) response to amines are largely affected by sequences variants
2023
Pacalon, Jody | Belloir, Christine | Fiorucci, Sébastien | Briand, Loïc | Topin, Jérémie | Institut de Chimie de Nice (ICN) ; Université Nice Sophia Antipolis (1965 - 2019) (UNS)-Institut de Chimie - CNRS Chimie (INC-CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UniCA) | Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA) ; Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Dijon ; Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro) | Université Bourgogne Franche-Comté [COMUE] (UBFC) | NeuroMod, Agence Nationale de la Recherche, Université Côte d'Azur, CNRS, Fondation Edmond Roudnitska.
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Показать больше [+] Меньше [-]Английский. The Trace Amine Associated Receptors (TAARs) are a family of chemosensory receptors that recognize volatile amines. These receptors are few in number and highly conserved, compared to regular olfactory receptors. Polymorphisms in the TAAR family can have a drastic impact on our perception of amine compounds. Our study combine numerical simulations with in vitro experiments to reveal the activation mechanisms of the human TAAR5 receptor. The study focused on the hTAAR5-S95P polymorphism, which is found at high frequency in Nordic countries. This mutation affects the perception of trimethylamine (TMA), making individuals less able to perceive the smell of rotten fish caused by this molecule. The study's 3D model captures the inability of the hTAAR5-S95P variant to be activated by TMA in vitro, as well as the activation of the receptor by different agonists. Long-scale molecular dynamics simulations were used to study the system bound to ligands with different efficacies, providing insight into the features of a prototypical active state of G protein-coupled receptors. The study has identified two specific features of the TAAR family that are responsible for the altered perception of TMA in individuals with this polymorphism.
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