title: Identification of an amyloid fibril forming peptide comprising residues 46-59 of apolipoprotein A-I.
abstract: 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-I(46-59), that retains the ability to form amyloid-like fibrils with cross-β structure. ApoA-I(46-59) corresponds closely to a conformationally extended segment in the crystal structure of apoA-IΔ(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.
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Yuan Qi
authors.initials: YQ
authors.lastname: Wong
authors.forename: Katrina J
authors.initials: KJ
authors.lastname: Binger
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Howlett
authors.forename: Michael D W
authors.initials: MD
authors.lastname: Griffin
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D028226:Amyloidosis, Familial / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D018360:Crystallography, X-Ray; D046529:Microscopy, Electron, Transmission; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D016632:Apolipoprotein A-I; D010446:Peptide Fragments