Abstract
Lipid membranes are known to influence the folding, aggregation, and fibril formation of a variety of amyloidogenic proteins. In some natively unstructured amylodogenic proteins such as α– synuclein and islet amyloid peptide, the formation of partially α– helical conformations upon membrane binding promotes the aggregation of proteins through exposure of highly amyloidogenic regions. We recently demonstrated that a G26R mutation, the first amyloidogenic mutation found in apolipoprotein A–I (apoA–I), facilitates aggregation and fibril formation of the N–terminal 1–83 fragment of apoA–I on lipid membranes through a partial destabilization of α– helical conformation. Here, we have reviewed the molecular mechanism of membrane-mediated aggregation and fibril formation of the amyloidogenic N–terminal fragment of apoA–I. We also briefly introduce the membrane–mediated aggregation behavior of α– synuclein that has similar lipid-binding property to apoA–I.
