Novel Structural Insights into GPCR-β-Arrestin Interaction and Signaling

G protein-coupled receptors (GPCRs) are major signal recognition and transmission units in the plasma membrane. The interaction of activated and phosphorylated GPCRs with the multifunctional adaptor proteins β-arrestins (βarrs) is crucial for regulation of their signaling and functional outcomes. Over the past few years, a range of structural, biochemical, and cellular studies have revealed novel insights into GPCR-βarr interaction and signaling. Some of these findings have come as a surprise and therefore have the potential to significantly refine the conceptual framework of the GPCR-βarr system. Here we discuss these recent advances with particular emphasis on biphasic GPCR-βarr interaction, the formation of GPCR-G-protein-βarr supercomplexes, and receptor-specific conformational signatures in βarrs. We also underline the emerging research areas that are likely to be at the center stage of investigations in the coming years.