Belloir, Christine

Briand, Loïc

Fiorucci, Sébastien

Pacalon, Jody

Topin, Jérémie

Résumé du poster Fri-P2-104 dans book of abstracts.International audienceVolatile amines are recognized by a family of chemosensory receptors: the Trace Amine Associated Receptors (TAARs). Compared to regular olfactory receptors, TAARs are few (6 receptors expressed in the olfactory epithelium) and highly conserved. Thus, polymorphisms in this family can drastically alter our perception of amine compounds. A joint approach of numerical simulations and in vitro experiments has revealed the activation mechanisms of hTAAR5. hTAAR5-S95P is a polymorphism found at high frequency in Nordic countries. People with this mutation have their perception of trimethylamine affected, making them less able to perceive the rotten fish smell caused by this molecule. Our 3D model captures both the inability of hTAAR5-S95P to be activated by trimethylamine (TMA) in vitro, and the activation of the receptor by different agonists. Long-scale molecular dynamics simulations of the system bound to ligands with different efficacies are performed and recover that the receptor is activated only when stimulated by agonists, capturing the features of a prototypical active state of GPCR. 2 specific features of the TAAR family were studied

Trace amine associated receptors (TAARs) response to amines are largely affected by sequences variants

Abstract

Similar works

Full text

Available Versions

HAL-uB