Phosphatidylethanolamine accelerates aggregation of the amyloidogenic N‐terminal fragment of apoA‐I

Abstract

Membrane lipid composition is known to influence aggregation and fibril formation of many amyloidogenic proteins. Here, we found that phosphatidylethanolamine (PE) accelerates aggregation of the N-terminal 1-83 fragment of an amyloidogenic G26R variant of apoA-I on lipid membranes. Circular dichroism and isothermal titration calorimetry measurements demonstrated that PE does not affect the α-helical structure and lipid binding property of apoA-I 1-83/G26R. Rather, fluorescence measurements indicated that PE induces more ordered lipid packing at the interfacial and acyl chain regions, providing more hydrophobic environments especially around the highly amyloidogenic regions in apoA-I on the membrane surface. These results suggest that PE promotes aggregation of the amyloidogenic N-terminal fragment of apoA-I on lipid membranes by inducing hydrophobic membrane environments.

On the Aggregation of Apolipoprotein A-I

“…HDL particles typically have a discoidal shape with a diameter of 7–13 nm [ 10 ] and are built up by a patch of a lipid bilayer with the lipid acyl chains at the edges shielded from water by a circumference belt of α-helical ApoA-I [ 11 , 12 ]. While the exact molecular triggers of the conversion from healthy lipid-protein co-aggregates, HDL particles, to pathological aggregates, plaques, is not yet understood, lipid oxidation and the concentration of lipids, including cholesterol, seems to play a role [ 13 , 14 , 15 , 16 ]. Other identified factors are mutations and truncations of the ApoA-I sequence.…”