The alpha-factor mating pheromone of Saccharomyces cerevisiae: a model for studying the interaction of peptide hormones and G protein-coupled receptors.
Mating in Saccharomyces cerevisiae is initiated by the secretion of diffusible peptide pheromones that are recognized by G protein-coupled receptors (GPCR). This review summarizes the use of the alpha-factor (WHWLQLKPGQPMY)--GPCR (Ste2p) interaction as a paradigm to understand the recognition between medium-sized peptide hormones and their cognate receptors. Studies over the past 15 years have indicated that the alpha-factor is bent around the center of the pheromone and that residues near the amine terminus play a central role in triggering signal transduction. The bend in the center appears not to be rigid and this flexibility is likely necessary for conformational changes that occur as the receptor switches from the inactive to active state. The results of synthetic, biological, biochemical, molecular biological, and biophysical analyses have led to a preliminary model for the structure of the peptide bound to its receptor. Antagonists for Ste2p have changes near the N-terminus of alpha-factor, and mutated forms of Ste2p were discovered that appear to favor binding of these antagonists relative to agonists. Many features of this yeast recognition system are relevant to and have counterparts in mammalian cells.
Naider
Fred
F
Department of Chemistry, College of Staten Island and Institute for Macromolecular Assemblies of The City University of New York, Staten Island, NY 10314, USA. naider@postbox.csi.cuny.edu
Becker
Jeffrey M
JM
D000409:Alanine / Q000737:chemistry; D001665:Binding Sites; D001667:Binding, Competitive; D004305:Dose-Response Relationship, Drug; D005656:Fungal Proteins; D005800:Genes, Fungal; D006031:Glycosylation; D007455:Iodine / Q000737:chemistry; D007700:Kinetics; D008024:Ligands; D008027:Light; D008956:Models, Chemical; D008958:Models, Molecular; D009154:Mutation; D036361:Peptide Hormones / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry*; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D013053:Spectrophotometry; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000737:chemistry
D005656:Fungal Proteins; D008024:Ligands; D036361:Peptide Hormones; D010455:Peptides; D043562:Receptors, G-Protein-Coupled; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D014157:Transcription Factors; D007455:Iodine; D000409:Alanine