Functional Microswitches of Mammalian G Protein-Coupled Bitter-Taste Receptors [article]

Jérémie Topin, Cédric Bouysset, Yiseul Kim, MeeRa Rhyu, Sébastien Fiorucci, Jérôme Golebiowski
2020 bioRxiv   pre-print
Bitter taste receptors (TAS2Rs) are a poorly understood subgroup of G protein-coupled receptors (GPCR). No experimental structure of these receptors is available and key-residues controlling their function remain mostly unknown. Here, we have identified the functional microswitches that encode agonist sensing and downstream signaling mechanisms within TAS2Rs sequences. We thoroughly re-aligned the amino-acid sequences of the 25 human TAS2Rs considering residue conservations and all the
more » ... nd all the experimental data from the literature as constraints. As a test case, an accurate homology model of TAS2R16 was constructed and examined by site-directed mutagenesis and in vitro functional assays. Conserved motifs acting as microswitches during agonist-sensing and receptor activation were pinpointed by comparison with the current knowledge on class A GPCRs. Unravelling these sequence-function relationships is of utmost importance to streamline how TAS2Rs functions are encrypted in their sequence.
doi:10.1101/2020.10.23.348706 fatcat:bqsp26422ngmfmpjih2llomy34