Yeast α factor is processed from a larger precursor polypeptide: The essential role of a membrane-bound dipeptidyl aminopeptidase

Abstract Alpha factor mating pheromone is a peptide of 13 amino acids secreted by Saccharomyces cerevisiae α cells. Nonmating (sterile, or ste ) α-cell mutants bearing defects in the STE13 gene do not produce normal α factor, but release a collection of incompletely processed forms (α factor∗) that have a markedly reduced specific biological activity. The major α-factor∗ peptides have the structures H 2 N-GluAlaGluAla-α factor and H 2 N-AspAlaGluAla-α factor. The ste13 mutants lack a membrane-bound heat-stable dipeptidyl aminopeptidase (DPAPase A) that specifically cleaves on the carboxyl side of repeating -X-Ala- sequences. Absence of DPA-Pase A and the other phenotypes of a ste13 lesion cosegregate in genetic crosses. The cloned STE13 gene on a plasmid causes yeast cells to overproduce DPAPase A severalfold. A different cloned DNA segment, which weakly suppresses the ste13 defects, causes overproduction of a heat-labile activity (DPAPase B) by about tenfold. Other experiments indicate that DPAPase A action may be ratelimiting for α-factor maturation in normal α cells.