Fig. 3 PS1?BI1 complex exhibits no proteolytic activity toward the APP-C99 substrate. (A) PS1?BI1 complex failed to generate A?42 or A?40 using the APP-C99 substrate. The spectroscopic reading of A?40 by ?-secretase is normalized as 1.0. The PS1?BI1 complex has no detectable activity. (B) Recombinant BI1 protein exhibits no apparent impact on the production of A?42 or A?40 by ?-secretase in vitro. Compared with ?-secretase, the amount of BI1 varied from equimolar to a 20-fold molar excess. (C) BI1 at a 200-fold molar excess inhibited the production of A?42 or A?40 by ?-secretase. The effect is specific because the control protein, AQP-1, at a 200-fold molar excess exhibited no impact on the proteolytic activity of ?-secretase.
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