Edbauer Dieter, Winkler Edith, Regula Joerg T, Pesold Brigitte, Steiner Harald, Haass Christian
Adolf-Butenandt-Institute, Department of Biochemistry, Laboratory for Alzheimer's and Parkinson's Disease Research, Ludwig-Maximilians-University, 80336 Munich, Germany.
Nat Cell Biol. 2003 May;5(5):486-8. doi: 10.1038/ncb960.
gamma-Secretase is a membrane protein complex with an unusual aspartyl protease activity that catalyses the regulated intramembranous cleavage of the beta-amyloid precursor protein (APP) to release the Alzheimer's disease (AD)-associated amyloid beta-peptide (Abeta) and the APP intracellular domain (AICD). Here we show the reconstitution of gamma-secretase activity in the yeast Saccharomyces cerevisiae, which lacks endogenous gamma-secretase activity. Reconstituted gamma-secretase activity depends on the presence of four complex components including presenilin (PS), nicastrin (Nct), APH-1 (refs 3-6) and PEN-2 (refs 4, 7), is associated with endoproteolysis of PS, and produces Abeta and AICD in vitro. Thus, the biological activity of gamma-secretase is reconstituted by the co-expression of human PS, Nct, APH-1 and PEN-2 in yeast.
γ-分泌酶是一种具有独特天冬氨酸蛋白酶活性的膜蛋白复合物，它催化β-淀粉样前体蛋白（APP）的膜内裂解，释放出与阿尔茨海默病（AD）相关的淀粉样β肽（Aβ）和APP细胞内结构域（AICD）。在此我们展示了在缺乏内源性γ-分泌酶活性的酿酒酵母中γ-分泌酶活性的重建。重建的γ-分泌酶活性依赖于包括早老素（PS）、尼卡斯特林（Nct）、APH-1（参考文献3 - 6）和PEN-2（参考文献4、7）在内的四种复合物成分的存在，与PS的内蛋白水解作用相关，并在体外产生Aβ和AICD。因此，γ-分泌酶的生物学活性通过在酵母中共表达人PS、Nct、APH-1和PEN-2得以重建。
