Biochemical approaches to G protein-coupled receptors dimerization.

Abstract

GPCR dimers and receptor mosaics are distinct pharmacological entities that can be targeted by specific ligands, including bivalent ligands, thus GPCR dimerization is a well-known concept. GPCR oligomerization can be studied with biochemical, biophysical, and computational methods. Here, we review classical and novel biochemical approaches to investigate this phenomenon. We discuss protomer co-expression, co-immunoprecipitation, heteromer-specific antibodies, proximity ligation assay, APEX2-MS proximity assay, receptor mutants and chimeras, radiation inactivation studies, cross-linking studies, and trans-complementation studies. For each approach, the basis of the technique is summarized, followed by an extensive list of its applications. This review is a comprehensive resource for biochemists and molecular biologists working in the field of GPCR oligomerization, as well as for scientists interested in GPCR drug design and discovery.