Paired basic residues have been observed as sites of proteolytic processing of prohormones in a wide range of eukaryotic species1-3. This strongly suggests that proteases exhibiting specificity towards paired basic residues may be involved in prohormone processing, but candidate enzymes have not so far been identified. Yeast Saccharomyces cerevisiae α-cells synthesize and secrete α-mating factor, a peptide of 13 amino acids 4,5, the processing of which from a larger precursor involves cleavage at paired basic residues (-Lys-Arg-)3,6. We have therefore used them as a simple model system for the study of prohormone processing and report here the identification, in cell lysates, of a novel protease which specifically recognizes and cleaves the peptide bonds between consecutive basic residues. The purified enzyme, which we have called pro-pheromone-convertase Y, has a molecular weight (MW) of around 43,000. It cleaves various peptide substrates at paired basic residues, but not at single basic residues, implying it is distinct from trypsin-like proteases. Its unique substrate specificity suggests the enzyme may be involved in propheromone processing in vivo.
ASJC Scopus subject areas