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Int J Biol Macromol. 2015 Aug;79:711-8. doi: 10.1016/j.ijbiomac.2015.05.032. Epub 2015 Jun 3.

Chameleon 'aggregation-prone' segments of apoA-I: A model of amyloid fibrils formed in apoA-I amyloidosis.

Author information

1
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece.
2
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC 3010, Australia.
3
Department of Cell Biology and Biophysics, Faculty of Biology, University of Athens, Panepistimiopolis, Athens 157 01, Greece. Electronic address: veconom@biol.uoa.gr.

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.

KEYWORDS:

Amyloid fibrils; Familial apolipoprotein A-I amyloidosis; “Aggregation-prone” peptide-analogues

PMID:
26049118
DOI:
10.1016/j.ijbiomac.2015.05.032
[Indexed for MEDLINE]

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