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bioRxiv · 10.1101/2020.10.23.348706

Functional Microswitches of Mammalian G Protein-Coupled Bitter-Taste Receptors

Topin, J.·Bouysset, C.·Kim, Y.·Rhyu, M.·Fiorucci, S.·Golebiowski, J.
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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 clarify sequence-function relationships and identify the functional molecular switches that encode agonist sensing and downstream signaling mechanisms within mammalian TAS2Rs sequences. ClassificationBiological sciences, Computational biology, and bioinformatics

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Topin, J., Bouysset, C., Kim, Y., Rhyu, M., Fiorucci, S., Golebiowski, J.. 2020-10-23. Functional Microswitches of Mammalian G Protein-Coupled Bitter-Taste Receptors. https://doi.org/10.1101/2020.10.23.348706

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