Two types of alpha-factor receptor determinants for pheromone specificity in the mating-incompatible yeasts S. cerevisiae and S. kluyveri.
The specificity of mating-pheromone systems helps prevent mating between different species of yeast. The mechanism of specificity of G protein-coupled receptors in other organisms may be similar. To determine the structural basis of species discrimination between alpha-factor variants, small extracellular segments of the Saccharomyces cerevisiae alpha-factor receptor were substituted with residues from the Saccharomyces kluyveri alpha-factor receptor. Three substitutions altered specificity towards S. cerevisiae and S. kluyveri alpha-factor pheromone peptides. A substitution at residues 47-49 affected specificity for pheromone binding but not for pheromone activation of response. Substitution of residues 267-269 affected pheromone specificity for activation of cellular responses, but not for pheromone binding (under the assay conditions used). Substitution of residues 104-123 modestly affected both types of specificity. These results suggest two distinct types of receptor/ligand specificity (perhaps corresponding to ligand binding to G protein-coupled or uncoupled conformational states of the receptor) that evolved independently as S. cerevisiae and S. kluyveri diverged as species.
Sen
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Department of Cell Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
Shah
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Marsh
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D001665:Binding Sites; D005656:Fungal Proteins / Q000378:metabolism*; D000072235:Mating Factor; D010455:Peptides / Q000378:metabolism; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012440:Saccharomyces / Q000737:chemistry* / Q000145:classification; D012441:Saccharomyces cerevisiae / Q000737:chemistry*; D013045:Species Specificity; D013379:Substrate Specificity; D014157:Transcription Factors
D005656:Fungal Proteins; D010455:Peptides; D051964:Receptors, Mating Factor; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D000072235:Mating Factor