Methods to monitor the quaternary structure of G protein-coupled receptors

A wide range of approaches has been applied to examine the quaternary structure of G protein-coupled receptors, the basis of such protein-protein interactions and how such interactions might modulate the pharmacology and function of these receptors. These include coimmunoprecipitation, various adaptations of resonance energy transfer techniques, functional complementation studies and the analysis of ligand-binding data. Each of the available techniques has limitations that restrict interpretation of the data. However, taken together, they provide a coherent body of evidence indicating that many, if not all, G protein-coupled receptors exist and function as dimer/oligomers. Herein we assess the widely applied techniques and discuss the relative benefits and limitations of these approaches.