New insights into GPCR coupling and dimerisation from cryo-EM structures.

Over the past three years (2020-2022) more structures of GPCRs have been determined than in the previous twenty years (2000-2019), primarily of GPCR complexes that are large enough for structure determination by single-particle cryo-EM. This review will present some structural highlights that have advanced our molecular understanding of promiscuous G protein coupling, how a G protein receptor kinase and β-arrestins couple to GPCRs, and GPCR dimerisation. We will also discuss advances in the use of gene fusions, nanobodies, and F fragments to facilitate the structure determination of GPCRs in the inactive state that, on their own, are too small for structure determination by single-particle cryo-EM.