Structural mechanism of arrestin activation

The large and multifunctional family of G protein-coupled receptors (GPCRs) are regulated by a small family of structurally conserved Arrestin proteins. In order to bind an active GPCR, Arrestin must first be activated by interaction with the phosphorylated receptor C-terminus. Recent years have witnessed major developments in high-resolution crystal structures of pre-active arrestins and Arrestin or arrestin-derived peptides in complex with an active GPCR. Although each structure individually offers only a limited snapshot, taken together and interpreted in light of recent complementary functional data, they offer valuable insight into how Arrestin is activated by and couples to a phosphorylated active GPCR.