Structure-Activity Relationship of Mating Pheromone from the Fungal Pathogen Fusarium oxysporum

During sexual development ascomycete fungi produce two types of peptide pheromones termed a and . The pheromone from the budding yeast Saccharomyces cerevisiae, 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 pheromones from filamentous ascomycetes, which are significantly shorter and share almost no sequence similarity with the S. cerevisiae homolog. High resolution structure of synthetic -pheromone from the plant pathogenic ascomycete Fusarium oxysporum revealed the presence of a central -turn resembling that of its yeast counterpart. Disruption of the-fold by d-alanine substitution of the conserved central Gly(6)-Gln(7) residues or by random sequence scrambling demonstrated a crucial role for this structural determinant in chemoattractant activity. Unexpectedly, the growth inhibitory effect of F. oxysporum -pheromone was independent of the cognate G protein-coupled receptors Ste2 and of the central -turn but instead required two conserved Trp(1)-Cys(2) residues at the N terminus. These results indicate that, despite their reduced size, fungal -pheromones contain discrete functional regions with a defined secondary structure that regulate diverse biological processes such as polarity reorientation and cell division.