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

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. [ABSTRACT FROM AUTHOR]