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 L-arrestins couple to GPCRs, and GPCR dimerisation. We will also discuss advances in the use of gene fusions, nanobodies, and Fab 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.