Fig. 5
Modulation of ApoE4 behavior toward ApoE3-like upon its interaction with SPA. (A) Reduction of ApoE4 aggregation (yellow) by SPA (purple) to the level of ApoE3 aggregation (grey). The data were collected in Tris buffer at 37 oC and pH 7.4, representing averages of 3 replicates with standard deviation shown as error band. (B) Comparison of ApoE3 (grey) and ApoE4 (yellow) mean deuterium uptake after 60 s in the presence of SPA (purple). The red circle highlights the interaction of ApoE4 with SPA in the region corresponding to the loop connecting helices H2 and H3. The data were determined in 3 time intervals (60s, 120 and 600 s) and error bars represent standard error of mean (SEM). (C) Comparison of histogram distribution of the dihedral angle χ1 of the W34 in ApoE3M (grey), ApoE4M (yellow), and ApoE4M-SPA (purple). (D) Comparison of histogram distribution of the angle between the Cα atoms of residues 95-106-117 of the helix in ApoE3M (grey), ApoE4M (yellow), and ApoE4M-SPA (purple). (E) Comparison of the α-helical content of helix H3 in ApoE3M (grey), ApoE4M (yellow), and ApoE4M-SPA (purple) calculated by adaptive simulations. The critical residues in positions 112 and 123 discussed in the text are labelled.