Characterization of α2,6-Sialyltransferase Cleavage by Alzheimer's β-Secretase (BACE1)
| Autor: | Naoshi Dohmae, Kazuko Ogawa, Yasuhiro Hashimoto, Takaomi C. Saido, Yuriko Tachida, Norihiro Kotani, Shinobu Kitazume, Koji Takio, Ritsuko Oka, Minoru Suzuki |
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| Rok vydání: | 2003 |
| Předmět: |
Male
Sialyltransferase Recombinant Fusion Proteins Golgi Apparatus Peptide Transfection Biochemistry Alzheimer Disease Endopeptidases Exopeptidases mental disorders Amyloid precursor protein Animals Aspartic Acid Endopeptidases Rats Wistar beta-D-Galactoside alpha 2-6-Sialyltransferase Molecular Biology chemistry.chemical_classification Exopeptidase activity Binding Sites COS cells biology Hydrolysis Cell Biology Exopeptidase Molecular biology Fusion protein Sialyltransferases Rats Amino acid chemistry COS Cells biology.protein Amyloid Precursor Protein Secretases |
| Zdroj: | Journal of Biological Chemistry. 278:14865-14871 |
| ISSN: | 0021-9258 |
| Popis: | BACE1 is a membrane-bound aspartic protease that cleaves the amyloid precursor protein (APP) at the beta-secretase site, a critical step in the Alzheimer disease pathogenesis. We previously found that BACE1 also cleaved a membrane-bound sialyltransferase, ST6Gal I. By BACE1 overexpression in COS cells, the secretion of ST6Gal I markedly increased, and the amino terminus of the secreted ST6Gal I started at Glu(41). Here we report that BACE1-Fc chimera protein cleaved the A-ST6Gal I fusion protein, or ST6Gal I-derived peptide, between Leu(37) and Gln(38), suggesting that an initial cleavage product by BACE1 was three amino acids longer than the secreted ST6Gal I. The three amino acids, Gln(38)-Ala(39)-Lys(40), were found to be truncated by exopeptidase activity, which was detected in detergent extracts of Golgi-derived membrane fraction. These results suggest that ST6Gal I is cleaved initially between Leu(37) and Gln(38) by BACE1, and then the three-amino acid sequence at the NH(2) terminus is removed by exopeptidase(s) before secretion from the cells. |
| Databáze: | OpenAIRE |
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