Novel antagonist to agonist switch in chimeric G protein-coupled alpha-factor peptide receptors.
The alpha-factor analog desTrp1,Ala3 alpha-factor (dTA-alpha-factor) acts as an antagonist for both the S. cerevisiae alpha-factor receptor (c-alpha-FR) and the S. kluyveri alpha-factor receptor (k-alpha FR). Chimeric alpha-factor receptors in which a portion (residues 250-303) of the seven hydrophobic segments were derived from the k-alpha FR and the rest from c-alpha FR conferred potent activation of cellular responses by dTA-alpha-factor including induction of FUS1 expression without significantly affecting binding. Chimeric receptors with all hydrophobic segments derived from one receptor did not express sensitivity. We propose that dTA-alpha-factor represents an antagonist that that has an activation energy barrier to activating c-alpha FR and k-alpha FR but which retains a latent potential to act as an agonist.
Sen
M
M
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461.
Marsh
L
L
D001667:Binding, Competitive; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development; D019204:GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D007700:Kinetics; D000072235:Mating Factor; D010455:Peptides / Q000187:drug effects / Q000494:pharmacology*; D010675:Pheromones / Q000494:pharmacology*; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D012440:Saccharomyces / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000819:agonists / Q000037:antagonists & inhibitors
D010455:Peptides; D010675:Pheromones; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000072235:Mating Factor; D019204:GTP-Binding Proteins