Snapshot of Activated G Proteins at the Membrane: The Gα q -GRK2-Gßγ Complex

Abstract

G protein–coupled receptor kinase 2 (GRK2) plays a key role in the desensitization of G protein–coupled receptor signaling by phosphorylating activated heptahelical receptors and by sequestering heterotrimeric G proteins. We report the atomic structure of GRK2 in complex with Gα q and Gβγ, in which the activated Gα subunit of G q is fully dissociated from Gβγ and dramatically reoriented from its position in the inactive Gαβγ heterotrimer. Gα q forms an effector-like interaction with the GRK2 regulator of G protein signaling (RGS) homology domain that is distinct from and does not overlap with that used to bind RGS proteins such as RGS4.