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

Evaluating the functional relevance of mutant MC4R by ortholog sequence comparison and functional testing. Ala¹⁷⁵Thr within transmembrane domain 4 has been associated with obesity and positively tested for dysfunction (59–62). In amphibian, fish, and Western European hedgehog, MC4R Ala¹⁷⁵ is naturally substituted by Thr; accordingly, the human Ala¹⁷⁵Thr receptor protein has been examined and recently found to possess wild-type functionality (C Stäubert, H Römpler, and T Schöneberg; unpublished results).