Identification of a hyperactive mating pheromone of Saccharomyces cerevisiae.
The yeast mating pheromone a-factor is a farnesylated peptide [YIIKGVFWDPAC(Farnesyl)-OCH3] involved in the signal transduction cascade which leads to sexual conjugation of haploid cells. We have identified a synthetic analog of the a-factor, [D-Ala5] a-factor, which exhibits 4-6 fold greater biological activity than that of a-factor as judged by two different assay systems. In contrast, [L-Ala5] a-factor has 4-16 fold lower activity than wild-type a-factor. [D-Ala5] a-factor remains susceptible to cleavage by the yeast alpha-cell specific protease a-factorase, thereby ruling out increased activity due to greater stability. This report describes the first example of a hyperactive S. cerevisiae pheromone and may suggest a conformationally preferred form of this lipopeptide ligand.
Caldwell
G A
GA
Department of Microbiology, University of Tennessee, Knoxville 37996.
Wang
S H
SH
Dawe
A L
AL
Naider
F
F
Becker
J M
JM
D000595:Amino Acid Sequence; D003227:Conjugation, Genetic / Q000187:drug effects; D006238:Haploidy; D007700:Kinetics; D000072235:Mating Factor; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D010675:Pheromones / Q000494:pharmacology*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D013329:Structure-Activity Relationship
D009842:Oligopeptides; D010455:Peptides; D010675:Pheromones; D000072235:Mating Factor