title: Chameleon 'aggregation-prone' segments of apoA-I: A model of amyloid fibrils formed in apoA-I amyloidosis.
abstract: Apolipoprotein A-I (apoA-I) is the major component of high density lipoproteins and plays a vital role in reverse cholesterol transport. Lipid-free apoA-I is the main constituent of amyloid deposits found in atherosclerotic plaques, an acquired type of amyloidosis, whereas its N-terminal fragments have been associated with a hereditary form, known as familial apoA-I amyloidosis. Here, we identified and verified four "aggregation-prone" segments of apoA-I with amyloidogenic properties, utilizing electron microscopy, X-ray fiber diffraction, ATR FT-IR spectroscopy and polarized light microscopy. These segments may act as conformational switches, possibly controlling the transition of the α-helical apoA-I content into the "cross-β" architecture of amyloid fibrils. A structural model illuminating the structure of amyloid fibrils formed by the N-terminal fragments of apoA-I is proposed, indicating that two of the identified chameleon segments may play a vital part in the formation of amyloid fibrils in familial apoA-I amyloidosis.
authors.affiliation: Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece.
authors.forename: Nikolaos N
authors.initials: NN
authors.lastname: Louros
authors.affiliation: Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece.
authors.forename: Paraskevi L
authors.initials: PL
authors.lastname: Tsiolaki
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Michael D W
authors.initials: MD
authors.lastname: Griffin
authors.affiliation: Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Howlett
authors.affiliation: Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece.
authors.forename: Stavros J
authors.initials: SJ
authors.lastname: Hamodrakas
authors.affiliation: Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: veconom@biol.uoa.gr.
authors.forename: Vassiliki A
authors.initials: VA
authors.lastname: Iconomidou
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D028226:Amyloidosis, Familial / Q000378:metabolism / Q000473:pathology; D016632:Apolipoprotein A-I / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D066329:Protein Aggregates; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D012996:Solutions
chemical_list: C505693:APOA1 protein, human; D000682:Amyloid; D016632:Apolipoprotein A-I; D010455:Peptides; D066329:Protein Aggregates; D012996:Solutions
keywords: Amyloid fibrils; Familial apolipoprotein A-I amyloidosis; “Aggregation-prone” peptide-analogues