Role of the γ Subunit Prenyl Moiety in G Protein βγ Complex Interaction with Phospholipase Cβ

The G protein βγ complex regulates a wide range of effectors, including the phospholipase Cβ isozymes (PLCβs). Prenyl modification of the γ subunit is necessary for this activity. Evidence presented here supports a direct interaction between the G protein γ subunit prenyl group and PLCβ isozymes. A geranylgeranylated peptide corresponding to the C-terminal region of the γ subunit type, γ2, strongly inhibits stimulation of PLCβ2 and PLCβ3 activity by the βγ complex. This effect is specific because the same peptide has no effect on stimulation of PLCβ by an α subunit type, αq. Prenylation of the γ peptide is required for its inhibitory effect. When interaction of prenylated y subunit peptide to fluorophore-tagged PLCβ2 was examined by fluorescence spectroscopy, prenylated but not unprenylated peptide increased PLCβ2 fluorescence emission energy, indicating direct binding of the prenyl moiety to PLCβ. In addition, fluorescence resonance energy transfer was detected between fluorophore tagged PLCβ and wild type βγ complex but not an unprenylated mutant βγ complex. We conclude that a major function of the γ subunit prenyl group is to facilitate direct protein-protein interaction between the βγ complex and an effector, phospholipase Cβ.