Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2020.10.23.348706v1?rss=1 Authors: Topin, J., Bouysset, C., Kim, Y., Rhyu, M., Fiorucci, S., Golebiowski, J. Abstract: 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 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. Copy rights belong to original authors. Visit the link for more info