FIGURE 5.

Cryo-EM Structure of γ-secretase and progressive cleavage of APP transmembrane domain. (A) The cryo-EM structure of γ-secretase apo (left) and complexed with substrate C83 (right). Four subunits, Nct, PS1, Pen-2 and Aph-1, were indicated. Two conserved catalytic aspartates, D257 and D385, were shown as sticks in orange in the magnified graph. The APP substrate C83 was shown as cartoon in orange in the complex. (B) Schematic diagram of the progressive cleavage sites of γ-secretase on substrate C99.