Molecular determinants of GPCR oligomerization

Abstract

G protein-coupled receptors (GPCRs) have been shown to associate into dimers and oligomers in a receptor-specific manner, but the molecular determinants that control and modulate receptor association are less well understood. In this chapter, we discuss the factors and molecular mechanisms underlying GPCR association. We have focused on the serotonin1A receptor to highlight the experimental and computational approaches to probe receptor association. Inherent structural characteristics determine the dimer states that are observed for the different GPCRs. Membrane composition, especially cholesterol concentration is a major determinant of GPCR association. Indirect effects arising from membrane perturbations have been shown to modulate oligomerization. Interestingly, actin cytoskeleton has been shown to modulate GPCR association, but further work is required to understand the underlying mechanism. Unraveling the molecular basis of GPCR association is an important step toward designing better therapeutics and understanding its role in human health and disease.