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J Biol Chem

Title:		Molecular determinants of bioactivity of the Saccharomyces cerevisiae lipopeptide mating pheromone
Author(s):		Caldwell GA; Wang SH; Xue CB; Jiang Y; Lu HF; Naider F; Becker JM;
Address:		"Program in Cellular, Molecular, and Developmental Biology, University of Knoxville 37996-0845"
Journal Title:		J Biol Chem
Year:		1994
Volume:		269
Issue:		31
Page Number:		19817 - 19825
DOI:
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"The a-factor of Saccharomyces cerevisiae (YIIKGVF-WDPAC(Farnesyl)-OCH3) is a peptide pheromone in which post-translational modification with a farnesyl isoprenoid and carboxyl methyl group is required for export and bioactivity. Truncated and carboxyl-terminal modified analogs of the a-factor were synthesized in order to determine the effect of such modifications on bioactivity. Bioactivity studies on carboxyl-terminal analogs in which the chirality, the cysteine thioether, and the carboxyl ester were varied in an attempt to study the influence of topology on a-factor activity indicate that the hydrophobicity conferred by the farnesyl moiety and not its specific spatial orientation is a key determinant of a-factor potency. Analyses on truncated a-factors suggest that sequential removal of NH2-terminal residues leads to a gradient of potency loss, with some amino acids exhibiting a slightly greater contribution to bioactivity than others. Random oligonucleotide-targeted mutagenesis of the gene encoding a-factor was coupled to a biological screen to identify altered a-factor peptides which are secreted yet exhibit a loss of a-factor bioactivity. Transformants exhibiting this phenotype were examined to identify codon changes presumably responsible for the altered phenotype, thus indicating residues that may contribute significantly to a-factor bioactivity"
Keywords:		"Amino Acid Sequence Chromatography, High Pressure Liquid Chromatography, Thin Layer Mating Factor Molecular Sequence Data Mutagenesis, Site-Directed Peptide Fragments Peptides/chemistry/genetics/*metabolism Phenotype Protein Conformation Saccharomyces cer;"
Notes:		"MedlineCaldwell, G A Wang, S H Xue, C B Jiang, Y Lu, H F Naider, F Becker, J M eng GM-46520/GM/NIGMS NIH HHS/ Research Support, U.S. Gov't, P.H.S. 1994/08/05 J Biol Chem. 1994 Aug 5; 269(31):19817-25"