Characterization of alpha 2,6-sialyltransferase cleavage by Alzheimer's beta -secretase (BACE1).
Characterization of alpha 2,6-sialyltransferase cleavage by Alzheimer's beta -secretase (BACE1).
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发表时间：
2003
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通讯作者：
S. Kitazume;Y. Tachida;R. Oka;N. Kotani;Kazuko Ogawa;Minoru Suzuki;N. Dohmae;K. Takio;T. Saido;Y. Hashimoto
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作者：
S. Kitazume;Y. Tachida;R. Oka;N. Kotani;Kazuko Ogawa;Minoru Suzuki;N. Dohmae;K. Takio;T. Saido;Y. Hashimoto
BACE1是一种膜结合的天冬氨酸蛋白酶，可在β -分泌酶位点切割淀粉样蛋白前体蛋白（APP），这是阿尔茨海默病发病机制的关键步骤。我们之前发现BACE1还能裂解一种膜结合的唾液转移酶ST6Gal I。通过BACE1在COS细胞中的过表达，ST6Gal I的分泌明显增加，分泌的ST6Gal I的氨基端从Glu开始（41）。在这里，我们报道BACE1- fc嵌合体蛋白在Leu（37）和Gln（38）之间切割A-ST6Gal I融合蛋白或ST6Gal I衍生肽，表明BACE1的初始切割产物比分泌的ST6Gal I长3个氨基酸。通过外肽酶活性发现，Gln(38)-Ala(39)-Lys（40）这三个氨基酸被截断，这是在高尔基衍生膜部分的洗涤剂提取物中检测到的。这些结果表明，ST6Gal I最初在Leu（37）和Gln（38）之间被BACE1切割，然后在细胞分泌前被外肽酶去除NH(2)端的三个氨基酸序列。
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.