A single activity carboxyl methylates both farnesyl and geranylgeranyl cysteine residues

FEBS Letters

Johnson, Mark¹  Lane, Pamela¹  Stock, Jeff¹  Volker, Craig¹  Kwee, Cynthia¹ 

[1] Department of Chemistry and Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA

关键词: Protein carboxyl methylation;    GTP-binding protein;    Transforming protein;    Membrane attachment;    Prenylcysteine;    AFC;    N-acetyl-S-trans;    trans-farnesyl-L-cysteine;    FTA;    S-trans;    trans-farnesylthioacetic acid;    FTP;    S-trans;    trans-farnesyl-3-thiopropionic acid;    AGGC;    N-acetyl-S-all-trans-geranylgeranyl-L-cysteine;    GGTA;    S-all-trans-geranylgeranylthioacetic acid;    GGTP;    S-all-trans-geranylgeranyl-3-thiopropionic acid;    AGC;    N-acetyl-S-trans-geranyl-L-cysteine;    AdoMet;    S-adenosyl-L-methionine;    DTT;    dithiothreitol;   

DOI  :  10.1016/0014-5793(91)81415-5

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Members of the Ras superfamily of small GTP-binding proteins, γ-subunits of heterotrimeric G proteins and nuclear lamin B are subject to a series of post-translational modifications that produce prenylcysteine methylester groups at their carboxyl termini. The thioether-linked polyisoprenoid substituent can be either farnesyl (C₁₅) or geranylgeranyl (C₂₀). Small molecule prenylcysteine derivatives with either the C₁₅ or C₂₀ modification, such as N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC), S-trans,trans-farnesylthiopropionate (FTP), as well as the corresponding geranylgeranyl derivatives (AGGC and GGTP) are substrates for the carboxyl methyltransferase. Saccharomyces cerevisiae ste 14 mutants that lack RAS and a-factor carboxyl methyltransferase activity are also unable to methylate farnesyl and geranylgeranylcysteine derivatives. Moreover, C₂₀-substituted cysteine analogs directly compete for carboxyl methylation with the C₁₅-substituted cysteine analogs and vice versa. Finally, AGGC is even more effective than AFC as an inhibitor of Ras carboxyl methylation, despite the fact that Ras is methylated at a farnesylcysteine rather than a geranylgeranylcysteine residue.

【 授权许可】

Unknown