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dc.contributor.author Topin, Jérémie -
dc.contributor.author Bouysset, Cédric -
dc.contributor.author Pacalon, Jody -
dc.contributor.author Kim, Yiseul -
dc.contributor.author Rhyu, Mee-Ra -
dc.contributor.author Fiorucci, Sébastien -
dc.contributor.author Golebiowski, Jerome -
dc.date.accessioned 2021-11-05T08:30:09Z -
dc.date.available 2021-11-05T08:30:09Z -
dc.date.created 2021-11-04 -
dc.date.issued 2021-12 -
dc.identifier.issn 1420-682X -
dc.identifier.uri http://hdl.handle.net/20.500.11750/15760 -
dc.description.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. -
dc.language English -
dc.publisher Springer Science and Business Media Deutschland GmbH -
dc.title Functional molecular switches of mammalian G protein-coupled bitter-taste receptors -
dc.type Article -
dc.identifier.doi 10.1007/s00018-021-03968-7 -
dc.identifier.scopusid 2-s2.0-85117734290 -
dc.identifier.bibliographicCitation Cellular and Molecular Life Sciences, v.78, no.23, pp.7605 - 7615 -
dc.description.isOpenAccess FALSE -
dc.subject.keywordAuthor Bitter taste receptor -
dc.subject.keywordAuthor GPCR -
dc.subject.keywordAuthor Integrative structural biology -
dc.subject.keywordAuthor Structure–function relationships -
dc.subject.keywordPlus BINDING-SITE -
dc.subject.keywordPlus STRUCTURAL BASIS -
dc.subject.keywordPlus GPCR -
dc.subject.keywordPlus ACTIVATION -
dc.subject.keywordPlus REVEAL -
dc.subject.keywordPlus SENSITIVITY -
dc.subject.keywordPlus INSIGHTS -
dc.subject.keywordPlus DATABASE -
dc.subject.keywordPlus POCKET -
dc.citation.endPage 7615 -
dc.citation.number 23 -
dc.citation.startPage 7605 -
dc.citation.title Cellular and Molecular Life Sciences -
dc.citation.volume 78 -
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