Figure 5.

Comparative modeling and simulations of Aβn-γ-secretase complexes. (A) Schematic views of the modeling workflow and the top views (from the extracellular domain) of the binding poses of C99_ε49 (black), Aβ49_ζ46 (orange), Aβ46_γ43 (blue), Aβ43_γ40 (magenta), and Aβ40_γ37 (green). Membrane-anchoring residue K28 of each substrate is shown explicitly in the licorice representation. Zoom-in views of the C99_ε49 (upper) and Aβ40_γ37 (lower) show how the position of K28 influences the local distribution of the POPC phosphate groups with radial distance from K28 on the xy plane denoted by ρ_xy,K28. (B) View into the PS1 internal docking site in the Aβ40_γ37-bound γ-secretase (representation same as in Fig. 2C) (C). Distribution of the membrane electron density (left), membrane-anchoring residue K28 (middle), and substrate P6 (right) along the z axis in different Aβn-γ-secretase complexes. (D) Average z axis of the POPC phosphate on the extracellular side distributed along the radial distance ρ_xy,K28. (E) Probability density of the catalytic hydrogen bond distance. To see this figure in color, go online.