Structure and Function of Bitter Taste Receptors
Ravinder Abrol, Vaidehi Nagarajan, and William A. Goddard III
Materials and Process Simulation Center, Beckman Institute
California Institute of Technology
The gustatory system of mammals plays a crucial role in analyzing and discriminating foods as being harmful or
poisonous (by sensing bitter tasting compounds) from those that are beneficial or just delicious (by sensing sweet
tasting compounds). Mammals (especially humans) can distinguish among at least five taste types: sweet, bitter,
sour, salty, and umami. The sweet (T1R) and bitter (T2R) receptors that mediate the taste sensation belong to the
G-protein-coupled-receptor (GPCR) superfamily of seven-transmembrane (7TM) domain proteins. More than 25
human bitter receptors have been identified till now and recent deorphanization experiments suggest that bitter
ligands show differential activation of T2Rs. Till now only a third of these receptors have been deorphaned (i.e.,
have known agonists). We are currently trying to predict the structure of these deorphaned T2R receptors using
the MembStruk suite of programs. Preliminary results of this study for human T2R47 bitter receptor will be
presented. Once an ensemble of the receptor structures is generated, these will be docked with a number of
ligands to understand the differential response of T2Rs to these ligands. The structural insight gained will be used
to study other T2R receptors to predict possible agonists for them.