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

Stephan Born, Anat Levit, Masha Y. Niv, Wolfgang Meyerhof, Maik Behrens*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

88 Scopus citations

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 S853.29 and Q1755.40 have differential impactonstimulation with different agonists.Thefact that single point mutations lead toimprovedresponses forsomeagonistsand 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.

Original languageAmerican English
Pages (from-to)201-213
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number1
DOIs
StatePublished - 2 Jan 2013

Fingerprint

Dive into the research topics of 'The human bitter taste receptor TAS2R10 is tailored to accommodate numerous diverse ligands'. Together they form a unique fingerprint.

Cite this