Substrate specificity determinants in the farnesyltransferase beta-subunit.
Protein prenyltransferases catalyze the covalent attachment of isoprenoid lipids (farnesyl or geranylgeranyl) to a cysteine near the C terminus of their substrates. This study explored the specificity determinants for interactions between the farnesyltransferase of Saccharomyces cerevisiae and its protein substrates. A series of substitutions at amino acid 149 of the farnesyltransferase beta-subunit were tested in combination with a series of substitutions at the C-terminal amino acid of CaaX protein substrates Ras2p and a-factor. Efficient prenylation was observed when oppositely charged amino acids were present at amino acid 149 of the yeast farnesyltransferase beta-subunit and the C-terminal amino acid of the CaaX protein substrate, but not when like charges were present at these positions. This evidence for electrostatic interaction between amino acid 149 and the C-terminal amino acid of CaaX protein substrates leads to the prediction that the C-terminal amino acid of the protein substrate binds near amino acid 149 of the yeast farnesyltransferase beta-subunit.
Trueblood
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CE
Division of Genetics, Department of Molecular and Cell Biology, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.
Boyartchuk
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Rine
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D019883:Alkyl and Aryl Transferases / Q000235:genetics / Q000378:metabolism*; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D051231:Farnesyltranstransferase; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017368:Protein Prenylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology; D017386:Sequence Homology, Amino Acid; D013379:Substrate Specificity / Q000235:genetics
D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase