FIGURE 7.

Model of fibril formation of the N-terminal fragment of apoA-I mutant on lipid membranes. A, β-aggregation propensity and hydropathy of the N-terminal 1–83 residues of apoA-I. Residues 14–31 (13) and 46–59 (72), which are predicted to be β-aggregation prone regions, are shown as arrows. B, I, apoA-I 1–83/G26R has a predominantly random coil structure in solution. II, membrane binding induces the formation of α-helical structure probably in two regions including Trp8 and Trp50, respectively. α-Helix is depicted as cylinders. The possible formation of the α-helical structure around residue 26 (dotted cylinder) is inhibited by the G26R mutation. III and IV, association of apoA-I 1–83/G26R in partially helical states induces a high local concentration of the highly amyloidogenic region including Arg²⁶, leading to the transition to β-strand structure and acceleration of the intermolecular aggregation. The β-structure is shown as arrows.