Aspects of the structure of the D2 dopamine receptor

Significant new information on the D2 dopamine receptor has recently become available from a combination of protein chemical and molecular genetic analyses. Molecular genetic studies have shown the receptor to be a member of the family of receptors that are linked to G proteins and that have structures predicted to contain seven transmembrane domains. Two distinct species of D2 dopamine receptor have been found which may differ in their coupling to G proteins; their distributions have been mapped at the nucleic acid level. The D2 dopamine receptor has been purified from brain and anterior pituitary and characterized. Chemical modification of the brain receptor provides evidence for the importance of a carboxyl group that interacts with ligands at the receptor binding site. Here, Philip Strange discusses these points and proposes models of receptor-ligand interaction based on the conservation of several aspartic acid residues in receptors that bind cationic amines.