A novel protein engineering approach for investigating GPCR/ligand interactions

Abstract

Relaxin family peptide receptors (RXFP) 1 and 2, receptors for relaxin and insulin like peptide‐3 (INSL3) respectively, are G‐protein coupled receptors possessing large N terminal domains consisting of 10 leucine rich repeats (LRRs) and a low density lipoprotein Class A (LDLa) module. Ligand mediated activation requires primary binding to the LRRs as well as a secondary interaction involving the extracellular loops (ELs) of the transmembrane domains. The LDLa is necessary for activation possibly by a specific interaction with the ELs. The project aims to identify residues of RXFP1 and RXFP2 ELs involved in ligand/LDLa binding by mounting them onto a soluble protein scaffold..