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- W2085120816 abstract "Gamma-secretase is a membrane protein complex that catalyzes intramembrane proteolysis of a variety of substrates including the amyloid beta precursor protein of Alzheimer disease. Nicastrin (NCT), a single-pass membrane glycoprotein that harbors a large extracellular domain, is an essential component of the gamma-secretase complex. Here we report that overexpression of a single chain variable fragment (scFv) against NCT as an intrabody suppressed the gamma-secretase activity. Biochemical analyses revealed that the scFv disrupted the proper folding and the appropriate glycosyl maturation of the endogenous NCT, which are required for the stability of the gamma-secretase complex and the intrinsic proteolytic activity, respectively, implicating the dual role of NCT in the gamma-secretase complex. Our results also highlight the importance of the calnexin cycle in the functional maturation of the gamma-secretase complex. The engineered intrabodies may serve as rationally designed, molecular targeting tools for the discovery of novel actions of the membrane proteins." @default.
- W2085120816 created "2016-06-24" @default.
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- W2085120816 date "2009-10-01" @default.
- W2085120816 modified "2023-10-03" @default.
- W2085120816 title "Single Chain Variable Fragment against Nicastrin Inhibits the γ-Secretase Activity" @default.
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- W2085120816 doi "https://doi.org/10.1074/jbc.m109.055061" @default.
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