Structure/function relationship of the dopamine D2 receptors

The two isoforms of the D2 dopamine receptor D2A and D2B are products of the alternative splicing of the same gene. Both isoforms inhibit the formation of cAMP by interacting with the inhibitory guanine nucleotide binding proteins (G-proteins). However, the two isoforms have been shown to couple differentially with the different G-protein subtypes, the long isoform D2A coupling preferentially with Gi2. Using D2A dopamine receptor with mutations at specific amino acid positions in the 29-aa insert present in this isoform, we have identified the amino acids important for receptor-G-protein interaction.