Asymmetry of GPCR oligomers supports their functional relevance.

G protein-coupled receptors (GPCRs) can exist as dimers or as larger oligomeric clusters that enable intercommunication between different receptor protomers within the same complex. This phenomenon is observed at three distinct levels: (i) at the level of ligand binding where the activation of one protomer can allosterically inhibit or facilitate ligand binding to the second protomer; (ii) at the level of ligand-induced conformational switches, which occur between transmembrane domains of the two protomers; and (iii) within GPCR-associated protein complexes, either directly at the level of GPCR-interacting proteins or at further downstream levels of the complex. Intercommunication at these different levels introduces asymmetry within GPCR dimers wherein each protomer fulfills its specific task. In this review, we discuss how the asymmetric behavior of GPCRs highlights the advantage of oligomeric receptor organization and supports the functional relevance of GPCR dimerization.