Keeping G Proteins at Bay: A Complex Between G Protein―Coupled Receptor Kinase 2 and Gβ_γ

摘要

The phosphorylation of heptahelical receptors by heterotrimeric guanine nucle-otide―binding protein (C protein)―coupled receptor kinases (GRKs) is a universal regulatory mechanism that leads to desensitization of G protein signaling and to the activation of alternative signaling pathways. We determined the crystallographic structure of bovine GRK2 in complex with G protein β_1γ_2 subunits. Our results show how the three domains of GRK2―the RGS (regulator of G protein signaling) homology, protein kinase, and pleckstrin homology domains―integrate their respective activities and recruit the enzyme to the cell membrane in an orientation that not only facilitates receptor phosphorylation, but also allows for the simultaneous inhibition of signaling by Gα and Gβ_γ subunits.