BETA-AMYLOID PRECURSOR PROTEIN CLEAVAGE BY A MEMBRANE-BOUND PROTEASE
BETA-AMYLOID PRECURSOR PROTEIN CLEAVAGE BY A MEMBRANE-BOUND PROTEASE
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DOI：
10.1073/pnas.89.13.6075
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发表时间：
1992-07-01
影响因子：
11.1
通讯作者：
SISODIA, SS
中科院分区：
文献类型：
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作者：
SISODIA, SS
阿尔茨海默病中淀粉样斑块的主要成分是β-淀粉样蛋白，这是一种几乎等于4-kDa的肽，来源于淀粉样前体蛋白。先前的研究已经确定淀粉样前体蛋白在β-淀粉样肽内的蛋白水解裂解后分泌。本调查文件，在培养的细胞中，淀粉样前体蛋白被切割的质膜上的膜结合的内切蛋白酶和特异性的肽键水解在很大程度上是独立的前体的一级序列。裂解的主要决定因素似乎是α-螺旋构象和水解键与膜的距离（12-13个残基）。
The principal component of amyloid plaques in Alzheimer disease is beta-amyloid protein, an almost-equal-to 4-kDa peptide derived from amyloid precursor proteins. Previous studies have established that amyloid precursor proteins are secreted after proteolytic cleavage within the beta-amyloid peptide. The present investigation documents that, in cultured cells, amyloid precursor protein is cleaved on the plasma membrane by a membrane-bound endoprotease and that the specificity of peptide bond hydrolysis is largely independent of the primary sequence of the precursor. The principal determinants of cleavage appear to be an alpha-helical conformation and the distance (12-13 residues) of the hydrolyzed bond from membrane.