A Novel Membrane-associated Metalloprotease, Ste24p, Is Required for the First Step of NH2-terminal Processing of the Yeast a-Factor Precursor
Open Access
- 27 January 1997
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 136 (2), 271-285
- https://doi.org/10.1083/jcb.136.2.271
Abstract
Many secreted bioactive signaling molecules, including the yeast mating pheromones a-factor and α-factor, are initially synthesized as precursors requiring multiple intracellular processing enzymes to generate their mature forms. To identify new gene products involved in the biogenesis of a-factor in Saccharomyces cerevisiae, we carried out a screen for MATa-specific, mating-defective mutants. We have identified a new mutant, ste24, in addition to previously known sterile mutants. During its biogenesis in a wild-type strain, the a-factor precursor undergoes a series of COOH-terminal CAAX modifications, two sequential NH2-terminal cleavage events, and export from the cell. Identification of the a-factor biosynthetic intermediate that accumulates in the ste24 mutant revealed that STE24 is required for the first NH2-terminal proteolytic processing event within the a-factor precursor, which takes place after COOH-terminal CAAX modification is complete. The STE24 gene product contains multiple predicted membrane spans, a zinc metalloprotease motif (HEXXH), and a COOH-terminal ER retrieval signal (KKXX). The HEXXH protease motif is critical for STE24 activity, since STE24 fails to function when conserved residues within this motif are mutated. The identification of Ste24p homologues in a diverse group of organisms, including Escherichia coli, Schizosaccharomyces pombe, Haemophilus influenzae, and Homo sapiens, indicates that Ste24p has been highly conserved throughout evolution. Ste24p and the proteins related to it define a new subfamily of proteins that are likely to function as intracellular, membrane-associated zinc metalloproteases.Keywords
This publication has 61 references indexed in Scilit:
- Biogenesis of the Saccharomyces cerevisiae Mating Pheromone a-FactorThe Journal of cell biology, 1997
- Coatomer is essential for retrieval of dilysine-tagged proteins to the endoplasmic reticulumCell, 1994
- Families of zinc metalloproteasesFEBS Letters, 1994
- Coatomer Interaction with Di-Lysine Endoplasmic Reticulum Retention MotifsScience, 1994
- Families of metalloendopeptidases and their relationshipsFEBS Letters, 1992
- Basic local alignment search toolJournal of Molecular Biology, 1990
- A unique signature identifies a family of zinc‐dependent metallopeptidasesFEBS Letters, 1989
- A positive selection for mutants lacking orotidine-5′-phosphate decarboxylase activity in yeast: 5-fluoro-orotic acid resistanceMolecular Genetics and Genomics, 1984
- A simple method for displaying the hydropathic character of a proteinJournal of Molecular Biology, 1982
- Sterile host yeasts (SHY): A eukaryotic system of biological containment for recombinant DNA experimentsGene, 1979