Fig. 1.

Depiction of the D₂-V2.61(91)F mutant dopamine receptor as a monomer in a section of lipid bilayer. This figure represents the unfolded D_2L receptor showing the amino terminus (-NH₂) on the extracellular side and the carboxyl terminus (-CO₂H) on the intracellular side. Open circles (○) are used to indicate wild-type amino acids, whereas closed circles (• and ) are used to represent specific amino acids. As shown in the sequence, a valine-to-phenylalanine mutation at amino acid residue 91 (•) results in the D₂-V2.61(91)F mutant dopamine receptor. The purpose of the V2.61(91)F mutation is to modify the binding pocket of the D₂ receptor with the corresponding residue of the D₄ receptor and make it more accommodating to D₄-selective 1,4-DAPs (Simpson et al., 1999; Schetz et al., 2000; Kortagere et al., 2004; Floresca et al., 2005). Although most ligands bind an orthosteric binding site accessible from the extracellular face of the receptor (Floresca and Schetz, 2004), the sodium ion binds the receptor through an intracellular allosteric binding site formed by the interactions of transmembrane segments 2, 3, and 7 (Neve et al., 2001). Also shown in the diagram and the sequence is the relative position of the conserved negatively charged D2.50(80) that is critical for the interaction of sodium ions with the dopamine receptor (Neve et al., 1991, 2001).