Identification of an amyloid fibril forming peptide comprising residues 46–59 of apolipoprotein A-I》.pdfVIP

FEBS Letters 586 (2012) 1754–1758 journal homepage: www.FEBSL Identification of an amyloid fibril forming peptide comprising residues 46–59 of apolipoprotein A-I Yuan Qi Wong 2, Katrina J. Binger 1,2, Geoffrey J. Howlett, Michael D.W. Griffin ⇑ Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia a r t i c l e i n f o a b s t r a c t Article history: Apolipoprotein A-I (apoA-I) is deposited as amyloid within various major organs in hereditary apoA- Received 30 March 2012 I amyloidosis, and in arterial plaques associated with atherosclerosis. We have identified a tryptic Revised 2 May 2012 fragment of apoA-I, apoA-I46–59, that retains the ability to form amyloid-like fibrils with cross-b Accepted 3 May 2012 structure. ApoA-I46–59 corresponds closely to a conformationally extended segment in the crystal Available online 15 May 2012 structure of apoA-ID(185–243) and is located in the N-terminal region of apoA-I, which accumulates Edited by Barry Halliwell 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. Keywords: Protein misfolding Aggregation Structured summary of protein interactions: Peptide apoA-I and apoA-I bind by transmission