Active state structures of G protein-coupled receptors highlight the similarities and differences in the G protein and arrestin coupling interfaces

摘要

G protein-coupled receptors (GPCRs) regulate cellular signalling through heterotrimeric G proteins and arrestins in response to an array of extracellular stimuli. Structure determination of GPCRs in an active conformation bound to intracellular signalling proteins has proved to be highly challenging. Nonetheless, three new structures of GPCRs in an active state have been published during the last year, namely the adenosine A(2A) receptor (A(2A)R) bound to an engineered G protein, opsin bound to visual arrestin and the mu, opioid receptor (mu OR) bound to a G protein-mimicking nanobody. These structures have provided novel insight into the sequence of events leading to GPCR activation, and have highlighted both similarities and differences in the structure of the interface between GPCRs and different signalling proteins.