Interaction between G-protein β and γ subunit types is selective

Signal-transducing guanine nucleotide-binding proteins (G proteins) are made up of three subunits, α, β, and γ. Each of these subunits comprises a family of proteins. The rules for association between members of one family with members of another to form a multimer are not known; it is not clear whether associations are specific or nonspecific. Other than transducin (G(t)), the G protein in rod photoreceptors, most purified G proteins contain more than one subtype of β or γ subunits. The G(t) α subunit is associated only with β₁ and γ₁. It is not known whether this specificity is due to the differential expression of these subunit types in a cell type or due to intrinsically different affinities between different β and γ subunit types. We have used a transfected cell assay system to examine the association of the β₁, β₂, and β₃ proteins with the γ₁ and γ₂ proteins. Results show that γ₁ does not associate with β₂ and that β₃ does not associate with γ₁ or γ₂. Differences in affinities between types of G protein subunits will impose restrictions on the formation of certain heterotrimers and determine which G protein will be active in a cell. A chimeric molecule of β₁ and β₂ was used to broadly map the regions on these subunits that determine specificity of association.