Proteolytic processing and secretion of human beta-amyloid precursor protein in yeast. Evidence for a yeast secretase activity
| Autor: | H, Zhang, H, Komano, R S, Fuller, S E, Gandy, D E, Frail |
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| Rok vydání: | 1994 |
| Předmět: |
Molecular Sequence Data
Saccharomyces cerevisiae Chromatography Affinity Peptide Fragments Recombinant Proteins Amyloid beta-Protein Precursor Alzheimer Disease Endopeptidases Aspartic Acid Endopeptidases Humans Amino Acid Sequence Amyloid Precursor Protein Secretases Cloning Molecular Protein Processing Post-Translational Plasmids |
| Zdroj: | The Journal of biological chemistry. 269(45) |
| ISSN: | 0021-9258 |
| Popis: | Human beta-amyloid precursor protein (APP), the transmembrane precursor of the Alzheimer's disease beta-amyloid peptide, was expressed in the yeast Saccharomyces cerevisiae by fusion to prepro-alpha-factor. From analysis of protease-deficient yeast strains, the fusion protein underwent partial processing by Kex2 protease to generate full-length APP and a fraction of the molecules were degraded in the vacuole. A soluble APP ectodomain fragment bearing lumenal but not cytosolic epitopes was released into the media, indicating cleavage by a "membrane protein-solubilizing proteinase" or "secretase" activity. Yeast cells contained a C-terminal APP fragment that co-migrated with authentic C-terminal fragment derived from alpha-secretase cleavage of full-length APP in human cells. The N-terminal sequence of immunoaffinity purified C-terminal APP fragment from yeast was identical to that reported in mammalian and insect cells. These results demonstrate the existence of a secretase activity in yeast. Furthermore, this yeast secretase activity may be related to an APP processing activity present in metazoan cells. |
| Databáze: | OpenAIRE |
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