Allosteric Modulation of Family 3 GPCRs

Abstract

Abstract This article reviews recent advances towards an understanding of the transmembrane structure, its activation and binding sites of family 3 G‐Protein‐Coupled Receptors (3‐GPCRs). First, the prediction of their 3D structure via homology models based on the crystal structure of bovine rhodopsin will be discussed. Then, different kinetic mechanisms of ligand‐binding inside the heptahelical domain are presented before an overview of most common structural motifs of 3‐GPCR allosteric modulators will be given. Here, special focus lies in the characterization of their binding pocket within the transmembrane domain as well as their interaction with crucial amino acids. The overview of available mutation data inside the ligand‐binding domains as well as the influence of exchanged amino acids on the activity of different receptors leads to the question whether allosteric ligands of family 3 GPCRs bind to the same binding pocket and if there exists a common binding site of family 1 GPCRs and family 3 GPCRs.