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

Title
Functional molecular switches of mammalian G protein-coupled bitter-taste receptors
Authors
Topin, JérémieBouysset, CédricPacalon, JodyKim, YiseulRhyu, Mee-RaFiorucci, SébastienGolebiowski, Jerome
DGIST Authors
Topin, Jérémie; Bouysset, Cédric; Pacalon, Jody; Kim, Yiseul; Rhyu, Mee-Ra; Fiorucci, Sébastien; Golebiowski, Jerome
Issue Date
2021-10
Citation
Cellular and Molecular Life Sciences
Type
Article
Author Keywords
Bitter taste receptorGPCRIntegrative structural biologyStructure–function relationships
Keywords
BINDING-SITESTRUCTURAL BASISGPCRACTIVATIONREVEALSENSITIVITYINSIGHTSDATABASEPOCKET
ISSN
1420-682X
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. © 2021, The Author(s), under exclusive licence to Springer Nature Switzerland AG.
URI
http://hdl.handle.net/20.500.11750/15760
DOI
10.1007/s00018-021-03968-7
Publisher
Springer Science and Business Media Deutschland GmbH
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