Figure 3-31 Schematic drawing of the three-dimensional structure of the β₂ -adrenergic receptor (a prototypical G protein-coupled receptor), looking from the outside of the cell inward. Transmembrane domains (denoted by cylinders and numbered with roman numerals) coalesce to form a binding pocket. The correct orientation of the agonist norepinephrine is shown. Notice that agonist affinity is determined by specific amino acids located in transmembranes III, IV, and VII. These critical sites in transmembrane domains have been determined experimentally using chimeric receptor and mutagenesis approaches combined with sophisticated computer-modeling techniques. Ultimate confirmation of these structures will require crystallographic data, an approach that is being attempted by several laboratories. (Adapted from Stapelfeldt WH: The autonomic nervous system. In Schwinn DA [ed]: Scientific Principles of Anesthesia, vol 2. Philadelphia, Current Medicine, 1998.)