The Multispanning Membrane Protein Ste24p Catalyzes CAAX Proteolysis and NH2-terminal Processing of the Yeast a-Factor Precursor

• Published in: The Journal of biological chemistry Vol. 276; no. 50; pp. 46798 - 46806
• Main Authors: Tam, Amy, Schmidt, Walter K., Michaelis, Susan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 14.12.2001; American Society for Biochemistry and Molecular Biology
• Subjects: Amino Acid Sequence; Catalysis; Detergents - pharmacology; Dose-Response Relationship, Drug; Endopeptidase K - metabolism; Endopeptidases - metabolism; Genotype; Mass Spectrometry; Mating Factor; Membrane Proteins - metabolism; Metalloendopeptidases - metabolism; Methylation; Models, Biological; Molecular Sequence Data; Peptides - metabolism; Plasmids - metabolism; Proprotein Convertases; Protein Binding; Protein Precursors - metabolism; Protein Prenylation; Protein Structure, Tertiary; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins; Sequence Homology, Amino Acid; Zinc - metabolism; Zinc - pharmacology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M106150200

Saccharomyces cerevisiae Ste24p is a multispanning membrane protein implicated in the CAAXproteolysis step that occurs during biogenesis of the prenylated a-factor mating pheromone. Whether Ste24p acts directly as a CAAX protease or indirectly to activate a downstream protease has not yet been established. In this study, we demonstrate that purified, detergent-solubilized Ste24p directly mediates CAAX proteolysis in a zinc-dependent manner. We also show that Ste24p mediates a separate proteolytic step, the first NH2-terminal cleavage in a-factor maturation. These results establish that Ste24p functions both as a bona fideCOOH-terminal CAAX protease and as an a-factor NH2-terminal protease. Importantly, this study is the first to directly demonstrate that a eukaryotic multispanning membrane protein can possess intrinsic proteolytic activity.