Pérez-Sala D, Tan E W, Cañada F J, Rando R R
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115.
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3043-6. doi: 10.1073/pnas.88.8.3043.
Retinal transducin was previously shown to be farnesylated on its gamma subunit. This farnesylation reaction on a cysteine residue near the carboxyl terminus is followed by peptidase cleavage at the cysteine. Thus the modified cysteine becomes the carboxyl terminus. It is shown here that the free carboxyl group can be methylated by an S-adenosyl-L-methionine-dependent methyltransferase associated with the rod outer segment membranes. This process can be inhibited by S-adenosyl-L-homocysteine and sinefungin. Moreover, synthetic N-acetyl-S-farnesyl-L-cysteine, but not N-acetyl-L-cysteine, is a substrate for the enzyme. Rapid demethylation of N-acetyl-S-farnesyl-L-cysteine methyl ester can be observed in the membranes. Transducin is also enzymatically demethylated by the rod outer segment membranes. Moreover, the 23- to 29-kDa small G proteins are methylated and demethylated in this system. These data suggest that methylation/demethylation may play a regulatory role in visual signal transduction.
视网膜转导蛋白先前已被证明其γ亚基会发生法尼基化。在靠近羧基末端的半胱氨酸残基上发生的这种法尼基化反应之后，会在该半胱氨酸处进行肽酶切割。因此，修饰后的半胱氨酸成为羧基末端。本文表明，游离的羧基可被与视杆细胞外段膜相关的依赖S-腺苷-L-甲硫氨酸的甲基转移酶甲基化。该过程可被S-腺苷-L-高半胱氨酸和杀稻瘟菌素抑制。此外，合成的N-乙酰-S-法尼基-L-半胱氨酸，而非N-乙酰-L-半胱氨酸，是该酶的底物。在膜中可观察到N-乙酰-S-法尼基-L-半胱氨酸甲酯的快速去甲基化。转导蛋白也会被视杆细胞外段膜进行酶促去甲基化。此外，23至29 kDa的小G蛋白在该系统中会发生甲基化和去甲基化。这些数据表明，甲基化/去甲基化可能在视觉信号转导中发挥调节作用。
