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  • The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands.

The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands.

The Journal of neuroscience : the official journal of the Society for Neuroscience (2013-01-04)
Stephan Born, Anat Levit, Masha Y Niv, Wolfgang Meyerhof, Maik Behrens
ABSTRACT

Bitter taste is a basic taste modality, required to safeguard animals against consuming toxic substances. Bitter compounds are recognized by G-protein-coupled bitter taste receptors (TAS2Rs). The human TAS2R10 responds to the toxic strychnine and numerous other compounds. The mechanism underlying the development of the broad tuning of some TAS2Rs is not understood. Using comparative modeling, site-directed mutagenesis, and functional assays, we identified residues involved in agonist-induced activation of TAS2R10, and investigated the effects of different substitutions on the receptor's response profile. Most interestingly, mutations in S85(3.29) and Q175(5.40) have differential impact on stimulation with different agonists. The fact that single point mutations lead to improved responses for some agonists and to decreased activation by others indicates that the binding site has evolved to optimally accommodate multiple agonists at the expense of reduced potency. TAS2R10 shares the agonist strychnine with TAS2R46, another broadly tuned receptor. Engineering the key determinants for TAS2R46 activation by strychnine in TAS2R10 caused a loss of response to strychnine, indicating that these paralog receptors display different strychnine-binding modes, which suggests independent acquisition of agonist specificities. This implies that the gene duplication event preceding primate speciation was accompanied by independent evolution of the strychnine-binding sites.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Papaverine hydrochloride, powder
Sigma-Aldrich
Denatonium benzoate, ≥98%
Papaverine hydrochloride, European Pharmacopoeia (EP) Reference Standard
Supelco
Papaverine hydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
Chloramphenicol, VETRANAL®, analytical standard
Sigma-Aldrich
Strychnine
Sigma-Aldrich
Chloramphenicol, BioReagent, suitable for plant cell culture
Sigma-Aldrich
Chloramphenicol, ≥98% (HPLC)
Sigma-Aldrich
Chloramphenicol, meets USP testing specifications
Chloramphenicol, European Pharmacopoeia (EP) Reference Standard