Insights into the binding of phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor

Xevi Biarnés, Alessandro Marchiori, Alejandro Giorgetti, Carmela Lanzara, Paolo Gasparini, Paolo Carloni, Stephan Born, Anne Brockhoff, Maik Behrens, Wolfgang Meyerhof

Research output: Contribution to journalArticle

Abstract

Humans' bitter taste perception is mediated by the hTAS2R subfamily of the G protein-coupled membrane receptors (GPCRs). Structural information on these receptors is currently limited. Here we identify residues involved in the binding of phenylthiocarbamide (PTC) and in receptor activation in one of the most widely studied hTAS2Rs (hTAS2R38) by means of structural bioinformatics and molecular docking. The predictions are validated by site-directed mutagenesis experiments that involve specific residues located in the putative binding site and trans-membrane (TM) helices 6 and 7 putatively involved in receptor activation. Based on our measurements, we suggest that (i) residue N103 participates actively in PTC binding, in line with previous computational studies. (ii) W99, M100 and S259 contribute to define the size and shape of the binding cavity. (iii) W99 and M100, along with F255 and V296, play a key role for receptor activation, providing insights on bitter taste receptor activation not emerging from the previously reported computational models.

Original languageEnglish
Article numbere12394
JournalPLoS One
Volume5
Issue number8
DOIs
Publication statusPublished - 2010

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Biarnés, X., Marchiori, A., Giorgetti, A., Lanzara, C., Gasparini, P., Carloni, P., Born, S., Brockhoff, A., Behrens, M., & Meyerhof, W. (2010). Insights into the binding of phenyltiocarbamide (PTC) agonist to its target human TAS2R38 bitter receptor. PLoS One, 5(8), [e12394]. https://doi.org/10.1371/journal.pone.0012394