Sequence requirement for peptide recognition by rat brain p21ras protein farnesyltransferase.
AUTOR(ES)
Reiss, Y
RESUMO
We tested 42 tetrapeptides for their ability to bind to the rat brain p21ras protein farnesyltransferase as estimated by their ability to compete with p21Ha-ras in a farnesyltransfer assay. Peptides with the highest affinity had the structure Cys-A1-A2-X, where positions A1 and A2 are occupied by aliphatic amino acids and position X is occupied by a COOH-terminal methionine, serine, or phenylalanine. Charged residues reduced affinity slightly at the A1 position and much more drastically at the A2 and X positions. Effective inhibitors included tetrapeptides corresponding to the COOH termini of all animal cell proteins known to be farnesylated. In contrast, the tetrapeptide Cys-Ala-Ile-Leu (CAIL), which corresponds to the COOH termini of several neural guanine nucleotide binding (G) protein gamma subunits, did not compete in the farnesyl-transfer assay. Inasmuch as several of these proteins are geranylgeranylated, the data suggest that the two isoprenes (farnesyl and geranylgeranyl) are transferred by different enzymes. A biotinylated heptapeptide corresponding to the COOH terminus of p21Ki-rasB was farnesylated, suggesting that at least some of the peptides serve as substrates for the transferase. The data are consistent with a model in which a hydrophobic pocket in the protein farnesyltransferase recognizes tetrapeptides through interactions with the cysteine and the last two amino acids.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=50887Documentos Relacionados
- Cloning and expression of a cDNA encoding the alpha subunit of rat p21ras protein farnesyltransferase.
- Identification of a protein associated with p21ras by chemical crosslinking.
- p21ras is modified by a farnesyl isoprenoid.
- A mechanism for posttranslational modifications of proteins by yeast protein farnesyltransferase.
- p21ras activation via hemopoietin receptors and c-kit requires tyrosine kinase activity but not tyrosine phosphorylation of p21ras GTPase-activating protein.