0000000000528769

AUTHOR

Jody Pacalon

showing 2 related works from this author

Extracellular loop 2 of G protein-coupled olfactory receptors is critical for odorant recognition

2021

International audience; G protein-coupled olfactory receptors (ORs) enable us to detect innumerous odorants. They are also ectopically expressed in non-olfactory tissues and emerging as attractive drug targets. ORs can be promiscuous or highly specific, which is part of a larger mechanism for odor discrimination. Here, we demonstrate that the OR extracellular loop 2 (ECL2) plays critical roles in OR promiscuity and specificity. Using site-directed mutagenesis and molecular modeling, we constructed 3D OR models in which ECL2 forms a lid over the orthosteric pocket. We demonstrate using molecular dynamics simulations that ECL2 controls the shape and the volume of the odorant-binding pocket, m…

Protein Conformation alpha-HelicalOdorant bindingG protein[SDV]Life Sciences [q-bio]Mutagenesis (molecular biology technique)Molecular Dynamics SimulationLigandsReceptors OdorantBiochemistryMice[SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular BiologyExtracellularOlfactory receptorAnimalsHumans[SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular BiologyReceptorMolecular BiologyG protein-coupled receptorVirtual screeningmolecular modelingChemistryCell Biologyvirtual screeningLigand (biochemistry)Cell biology[SDV] Life Sciences [q-bio]Smell[SDV.AEN] Life Sciences [q-bio]/Food and NutritionOdorantsMutagenesis Site-Directedsite-directed mutagenesis[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
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Trace amine associated receptors (TAARs) response to amines are largely affected by sequences variants

2023

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. …

[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition[SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology
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