On the Mechanism of the Inhibition of Transducin Function by Farnesylcysteine Analogs
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- 作者：Craig A. Parish ; Derek P. Brazil ; and Robert R. Rando
- 刊名：Biochemistry
- 出版年：1997
- 出版时间：March 4, 1997
- 年：1997
- 卷：36
- 期：9
- 页码：2686 - 2693
- 全文大小：261K
- 年卷期：v.36,no.9(March 4, 1997)
- ISSN：1520-4995
文摘
The 
subunits of heterotrimeric G proteins areisoprenylated/methylated on their carboxytermini. The photoreceptor G protein, transducin, isfarnesylated/methylated at this position. Since theisoprenyl group is required for G protein function, it is of greatinterest to determine the mechanism bywhich the farnesyl group of T interacts with the other transducinsubunits and/or the activatedphotoreceptor, rhodopsin. Farnesylcysteine derivatives(N-acetyl-S-farnesyl-L-cysteine andfarnesylatedpeptides) have been previously shown to have effects on transducinactivity at high concentrations. Here,an extensive survey is done of farnesylcysteine analogs and other lipidmolecules, which are tested fortheir ability to inhibit GTP/GDP exchange in transducin catalyzed byphotolyzed rhodopsin. These studiesare carried out to determine the nature of the inhibition process.While it does not appear that thesemolecules exhibit the specificity which would characterize aligand-receptor type mechanism, the resultssuggest that these compounds are not acting in a nonspecificdetergent-like manner either. The mostlikely mode of action of farnesylcysteine analogs is that theyinterfere with the lipid-lipid based associationof T
and T
through the lipid modifications present on eachsubunit.
subunits of heterotrimeric G proteins areisoprenylated/methylated on their carboxytermini. The photoreceptor G protein, transducin, isfarnesylated/methylated at this position. Since theisoprenyl group is required for G protein function, it is of greatinterest to determine the mechanism bywhich the farnesyl group of T interacts with the other transducinsubunits and/or the activatedphotoreceptor, rhodopsin. Farnesylcysteine derivatives(N-acetyl-S-farnesyl-L-cysteine andfarnesylatedpeptides) have been previously shown to have effects on transducinactivity at high concentrations. Here,an extensive survey is done of farnesylcysteine analogs and other lipidmolecules, which are tested fortheir ability to inhibit GTP/GDP exchange in transducin catalyzed byphotolyzed rhodopsin. These studiesare carried out to determine the nature of the inhibition process.While it does not appear that thesemolecules exhibit the specificity which would characterize aligand-receptor type mechanism, the resultssuggest that these compounds are not acting in a nonspecificdetergent-like manner either. The mostlikely mode of action of farnesylcysteine analogs is that theyinterfere with the lipid-lipid based associationof T and T through the lipid modifications present on eachsubunit.