Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl-protein transferases

Kohl, N. E., Diehl, R. E., Schaber, M. D., Rands, E., Soderman, D. D., He, B., Moores, S. L., Pompliano, D. L., Ferro-Novick, S., Powers, S. (October 1991) Structural homology among mammalian and Saccharomyces cerevisiae isoprenyl-protein transferases. Journal of Biological Chemistry, 266 (28). pp. 18884-8. ISSN 0021-9258



Farnesyl-protein transferase (FTase) purified from rat or bovine brain is an alpha/beta heterodimer, comprised of subunits having relative molecular masses of approximately 47 (alpha) and 45 kDa (beta). In the yeast Saccharomyces cerevisiae, two unlinked genes, RAM1/DPR1 (RAM1) and RAM2, are required for FTase activity. To explore the relationship between the mammalian and yeast enzymes, we initiated cloning and immunological analyses. cDNA clones encoding the 329-amino acid COOH-terminal domain of bovine FTase alpha-subunit were isolated. Comparison of the amino acid sequences deduced from the alpha-subunit cDNA and the RAM2 gene revealed 30% identity and 58% similarity, suggesting that the RAM2 gene product encodes a subunit for the yeast FTase analogous to the bovine FTase alpha-subunit. Antisera raised against the RAM1 gene product reacted specifically with the beta-subunit of bovine FTase, suggesting that the RAM1 gene product is analogous to the bovine FTase beta-subunit. Whereas a ram1 mutation specifically inhibits FTase, mutations in the CDC43 and BET2 genes, both of which are homologous to RAM1, specifically inhibit geranylgeranyl-protein transferase (GGTase) type I and GGTase-II, respectively. In contrast, a ram2 mutation impairs both FTase and GGTase-I, but has little effect on GGTase-II. Antisera that specifically recognized the bovine FTase alpha-subunit precipitated both bovine FTase and GGTase-I activity, but not GGTase-II activity. Together, these results indicate that for both yeast and mammalian cells, FTase, GGTase-I, and GGTase-II are comprised of different but homologous beta-subunits and that the alpha-subunits of FTase and GGTase-I share common features not shared by GGTase-II.

Item Type: Paper
Uncontrolled Keywords: *Alkyl and Aryl Transferases Amino Acid Sequence Animals Base Sequence Cattle Cloning, Molecular Dna Immunoblotting Mammals Molecular Sequence Data Precipitin Tests Saccharomyces cerevisiae/*enzymology Sequence Alignment Transferases/*chemistry/genetics/metabolism
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification
organism description > yeast
CSHL Authors:
Communities: CSHL labs > Powers lab
Depositing User: Matt Covey
Date: 5 October 1991
Date Deposited: 25 Feb 2014 21:03
Last Modified: 25 Feb 2014 21:03
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