How GPCRs Engage GPCR Kinases in the First Step of Homologous Desensitization

G protein-coupled receptor (GPCR) kinases (GRKs) phosphorylate activated GPCRs, priming them for arrestin binding and internalization. How GRKs recognize these receptors is unknown, but most studies indicate that a conserved region at their extreme N-terminus key. Herein we report the cryo-EM structure of light rhodopsin (Rho∗) in complex with kinase (GRK1) along supporting functional confirm key interactions. The prominent interaction GRK1 N-terminus, which distinct from other recently proposed models GRK-GPCR complexes. domain adopts an active conformation appears to result displacement GRK regulator protein signaling (RGS) homology domain. Our data therefore provides model not only how engage are by and, also selectivity might occur GPCRs.