Unnatural amino acid receptor incorporation as a photoaffinity tool for GPCR heteromer signaling studies

Abstract

Class A G protein-coupled receptors (GPCRs) have been reported by multiple groups to form receptor heteromers and serve as allosteric regulators of one another. Yet their mere existence has become a highly contested topic. We have employed a minimally invasive approach of introducing unnatural amino acids (UAAs), using amber codon suppression, at strategic positions predicted to form the heteromeric interface of the dopamine 2 (D2) and serotonin 2A (2A) receptor (R) heteromer that has been implicated in schizophrenia.