Specificity of G protein β and γ subunit interactions

Multiple heterotrimeric guanine nucleotide binding protein (G protein) subunits have evolved to couple a large variety of receptors to intracellular effectors. G protein βγ subunits are essential for efficient coupling of α subunits to receptors, and they are also important for modulation of effectors. Several different β and γ subunits exist, but it is not known whether all possible combinations of β and γ can form functional dimers. To answer this question, we have compared the ability of in vitro translated β₁, β₂, and β₃ to form dimers with either γ₁ or γ₂. Dimerization was monitored by gel filtration, resistance to tryptic digestion, and chemical cross-linking. The results indicate that β₁ binds both γ subunits, β₂ binds only γ₂, and β₃ will bind neither γ₁ or γ₂. Hence, the occurrence of βγ dimers may be partially regulated by the ability of the subunits to associate. Specificity of dimerization might allow cells to co-express multiple β and γ subunits while maintaining efficient and specific signal transduction.