Shaky ground - The nature of metastable GPCR signalling complexes

Abstract

How G protein-coupled receptors (GPCR) interact with one another remains an area of active investigation. Obligate dimers of class C GPCRs such as metabotropic GABA and glutamate receptors are well accepted, although whether this is a general feature of other GPCRs is still strongly debated. In this review, we focus on the idea that GPCR dimers and oligomers are better imagined as parts of larger metastable signalling complexes. We discuss the nature of functional oligomeric entities, their stabilities and kinetic features and how structural and functional asymmetries of such metastable entities might have implications for drug discovery. This article is part of the Special Issue entitled 'Receptor heteromers and their allosteric receptor-receptor interactions'.

Keywords: G protein-coupled receptors; GPCRs; Oligomerization; Receptor mosaics; Signalling complexes; Specificity.