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Journal Articles Cellular and Molecular Life Sciences Year : 2021

Functional molecular switches of mammalian G protein-coupled bitter-taste receptors

Abstract

Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCRs). The experimental structure of these receptors has yet to be determined, and key-residues controlling their function remain mostly unknown. We designed an integrative approach to improve comparative modeling of TAS2Rs. Using current knowledge on class A GPCRs and existing experimental data in the literature as constraints, we pinpointed conserved motifs to entirely re-align the amino-acid sequences of TAS2Rs. We constructed accurate homology models of human TAS2Rs. As a test case, we examined the accuracy of the TAS2R16 model with site-directed mutagenesis and in vitro functional assays. This combination of in silico and in vitro results clarifies sequence-function relationships and proposes functional molecular switches that encode agonist sensing and downstream signaling mechanisms within mammalian TAS2Rs sequences.

Dates and versions

hal-02544670 , version 1 (16-04-2020)

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Jérémie Topin, Cédric Bouysset, Jody Pacalon, Yiseul Kim, Meera Rhyu, et al.. Functional molecular switches of mammalian G protein-coupled bitter-taste receptors. Cellular and Molecular Life Sciences, 2021, 78, pp.7605-7615. ⟨10.1007/s00018-021-03968-7⟩. ⟨hal-02544670⟩
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