Regulators of G-protein signaling (RGS) proteins enhance the intrinsic GTPase activity of G protein α (Gα) subunits and are vital for proper signaling kinetics downstream of G protein–coupled receptors (GPCRs). R7 subfamily RGS proteins specifically and obligately dimerize with the atypical G protein β5 (Gβ5) subunit through an internal G protein γ (Gγ)-subunit–like (GGL) domain. Here we present the 1.95-Å crystal structure of the Gβ5–RGS9 complex, which is essential for normal visual and neuronal signal transduction. This structure reveals a canonical RGS domain that is functionally integrated within a molecular complex that is poised for integration of multiple steps during G-protein activation and deactivation
