G Protein-Coupled Time Travel: Evolutionary Aspects of GPCR Research

Distribution of missense mutations in the melanocortin type 4 receptor (MC4R). Like all GPCRs, the MC4R is composed of seven transmembrane domains connected by three intra- and three extracellular loops. Inactivating mutations in the MC4R are indicated in inherited forms of obesity. Amino acid substitutions at sixty positions have been found in obese humans (colored circles), but only half of missense mutations reveal a partial or complete loss of receptor function (blue circles).