Evolutionary conservation and functional impact of dopamine D2 receptor

Abstract

PurposeDopamine D2-like receptors (D2) mediate various effects of dopamine. Characterizing the structural and functional regions can contribute to understanding the mechanism of biological effects of dopamine. MethodsA large scale phylogeny was utilized to construct a comprehensive dataset of D2 receptor, the evolutionary conserved residues were calculated at both super-family and sub-family (included human D2clade) levels, and then 3D structure of human D2 receptor (DRD2) was modeled to evaluate the significance of these conserved residues and motifs linked with structural stability, genetic variants, functional activation, protein interaction and drug binding. ResultsAll the drug binding sites and important protein-complex binding motifs showed evolutionary super-family conservation. However, genetic variants linked to different diseases all belonged to sub-family conservation. The extra cellular loop (ECL3) domain consisted of both super-family and sub-family conserved residues. ConclusionsSub-family conserved residues probably play a vital role in the incidence and progression of diseases.