New Hypotheses for the GPCR 3D Arrangement Based on a Molecular Model of the Human Sweet-taste Receptor

A molecular model of the human sweet-taste receptor has been inferred from superpositions of 3D maps of sweetener interaction sites (themselves previously deduced from extensive structure-activity relationship studies on highly potent sweeteners) onto three well-known G protein-coupled receptors (GPCRs)-rhodopsin, beta(2)- and alpha(2A)-adrenergic receptors-assumed to be linked by common evolutionary origins. The model gives new answers to old questions on the GPCR 3D structure, such as on the orientation and arrangement of the binding helices, their interaxial distances, radial orientations and relative heights. The model should be useful as a new approach to the rational design of drugs.