The Predicted 3D Structure of Bitter Taste Receptors, TAS2R38 Based on a BiHelix and SuperBiHelix Methodologies

Abstract

TAS2R38 bitter taste receptors are seven-transmembrane (TM) domain G protein-coupled receptors (GPCRs) that can respond to bitter compounds such as Phenylthiocarbamide (PTC). We would like to understand the nature of the binding that is what aspect of the ligand interacting with the binding site leads to signal sent to the cortex. There are no direct determinations of the 3D structure of taste receptors; hence we use the new BiHelix and SuperBiHelix methods to predict the 3D structures of the TAS2R38 bitter taste receptors, which we chose because there is ample experimental data on how perception is related to the ligand and to mutations. These methods use a template to provide starting points for the structures and we tested four templates β1 Adrenergic Receptor (tβ1AR), β2 Adrenergic Receptor (hβ2AR), Bovine Rhodopsin and A_(2A) Adenosine Receptor (hAA_(2A)R). We found the tβ1AR template is more appropriate for structural simulation of the bitter taste receptors. We predicted 3D structures of for four haplotypes PAV, AVI, AAI and PVV of the TAS2R38 bitter receptors. Our results illustrate that the residue 262 is involved in the interhelical hydrogen bond network stabilizing the structure in tasters (PAV, AAI and PVV) while it is not in non-tasters (AVI). Thus the hydrogen bond interaction between TM3 or TM5 and TM6 may play a role in activating this GPCR.

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