A novel type of G protein heterodimer: The Gbeta5-RGS complex

The fifth member of G protein β subunit family, Gβ5, has been previously shown to bind to a subfamily of regulators of G protein signaling (RGS) including RGS6, RGS7, RGS9 and RGS11. The interaction between Gβ5 and RGS proteins challenged the belief that all Gβ subunits exist as an obligatory heterodimer with G protein γ subunits. To determine if Gβ5 exists exclusively with RGS proteins or also with Gγ subunits, Gβ5 from brain extracts was partially purified and its native binding partners observed. The results demonstrated that unlike other Gβ subunits, Gβ5 does not bind to Gγ subunits in vivo, and instead is detected only as a heterodimer with a subfamily of RGS proteins. Gβ5-RGS7 was shown to exist in both cytosolic and membrane extracts from native tissues. This novel Gβ5-RGS heterodimer is the only form detected in cells, as monomeric forms of both proteins are rapidly degraded. Furthermore, the Gβ5-RGS7 dimer acts to attenuate Gαq signaling in cells due to a direct protein-protein interaction of the dimer with Gαq.