Identification of an amyloid fibril forming peptide comprising residues 46-59 of apolipoprotein A-I

Apolipoprotein A-I (apoA-I) is deposited as amyloid within various major organs in hereditary apoA-I amyloidosis, and in arterial plaques associated with atherosclerosis. We have identified a tryptic fragment of apoA-I, apoA-I46-59, that retains the ability to form amyloid-like fibrils with cross-beta structure. ApoA-I46-59 corresponds closely to a conformationally extended segment in the crystal structure of apoA-I Delta(185-243) and is located in the N-terminal region of apoA-I, which accumulates in hereditary apoA-I amyloidosis. Our results provide direct experimental evidence that this region of apoA-I is amyloidogenic and integral to initiation and propagation of amyloid formation by the protein.