The γ polypeptide of brain G-proteins is carboxyl methylated when the purified βγ subunit complex is reconstituted with S-adenosyl-[3H-methyl]-L-methionine and a methyltransferase present in detergent-stripped brain membranes. By Chromatographic analysis of the 3H-amino acid generated by exhaustive proteolysis and performic acid oxidation of the 3H-methylated βγ complex, we show that this modification occurs on the α-carboxyl group of a C-terminal cysteine residue. Our result suggests that brain G-proteins may undergo multiple covalent modification steps, including proteolytic removal of the three terminal amino acids from the predicted common C-terminal Cys-Xaa-Xaa-Xaa sequence, and the methyl esterification of the resulting terminal cysteine residue. This modification is likely to be associated with lipidation at the sulfhydryl group of the same cysteine, which would explain the tight membrane binding property of the brain βγ complex.
