A SITE ON ROD G-PROTEIN ALPHA-SUBUNIT THAT MEDIATES EFFECTOR ACTIVATION

The heterotrimeric guanine nucleotide binding proteins (G proteins) are activated by sensory or hormone receptors. In turn, the G proteins activate effector proteins such as adenylyl cyclase, cyclic guanosine 3',5'-monophosphate phosphodiesterase (cGMP PDE), phospholipase C, and potassium and calcium ion channels by mechanisms that are poorly understood. A site on the alpha-subunit of the G protein transducin (alpha(t)) has been identified that interacts with and activates cGMP phosphodiesterase, the effector enzyme in rod photoreceptors. A 22-amino acid peptide, corresponding to residues 293 to 314 from the COOH-terminal region of alpha(t), fully mimicked alpha(t) and potently activated PDE. This region is adjacent to the receptor activation domain; thus, the alpha-subunit of this G protein has a site for interaction with both its effector and receptor that maps near the COOH-terminus.