Document Detail


The Human Bitter Taste Receptor TAS2R10 Is Tailored to Accommodate Numerous Diverse Ligands.
MedLine Citation:
PMID:  23283334     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
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.
Authors:
Stephan Born; Anat Levit; Masha Y Niv; Wolfgang Meyerhof; Maik Behrens
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of neuroscience : the official journal of the Society for Neuroscience     Volume:  33     ISSN:  1529-2401     ISO Abbreviation:  J. Neurosci.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8102140     Medline TA:  J Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  201-13     Citation Subset:  IM    
Affiliation:
Department of Molecular Genetics, German Institute of Human Nutrition Potsdam-Rehbruecke, 14558 Nuthetal, Germany, and Institute of Biochemistry, Food Science, and Nutrition, Robert H. Smith Faculty of Agriculture, Food, and Environment, Hebrew University of Jerusalem, Rehovot 76100, Israel.
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