Structure-Activity Relationship of α Mating Pheromone from the Fungal Pathogen .

During sexual development ascomycete fungi produce two types of peptide pheromones termed a and α. The α pheromone from the budding yeast ， a 13-residue peptide that elicits cell cycle arrest and chemotropic growth， has served as paradigm for the interaction of small peptides with their cognate G protein-coupled receptors. However， no structural information is currently available for α pheromones from filamentous ascomycetes， which are significantly shorter and share almost no sequence similarity with the homolog. High resolution structure of synthetic α-pheromone from the plant pathogenic ascomycete revealed the presence of a central β-turn resembling that of its yeast counterpart. Disruption of the-fold by d-alanine substitution of the conserved central Gly-Gln residues or by random sequence scrambling demonstrated a crucial role for this structural determinant in chemoattractant activity. Unexpectedly， the growth inhibitory effect of α-pheromone was independent of the cognate G protein-coupled receptors Ste2 and of the central β-turn but instead required two conserved Trp-Cys residues at the N terminus. These results indicate that， despite their reduced size， fungal α-pheromones contain discrete functional regions with a defined secondary structure that regulate diverse biological processes such as polarity reorientation and cell division.