Understanding how ligands and regulatory proteins interact with dopamine receptors is critical for developing targeted therapies and advancing knowledge of central nervous system function. This dissertation investigated the structural basis of pharmacological selectivity between D1 and D2 dopamine receptors and identified arrestin‑binding sites on D2 and D3 receptors. Site‑directed mutagenesis, ligand binding assays, and molecular modeling revealed key residues that influence ligand specificity by shaping the receptor binding pocket. Complementary biochemical and cellular studies identified intracellular regions important for arrestin binding and receptor internalization, including specific residues within the second and third intracellular loops. Together, these findings clarify molecular determinants of dopamine receptor signaling and regulation.
