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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Amyloid / chemistry*
  • Amyloidosis, Familial / metabolism
  • Amyloidosis, Familial / pathology
  • Apolipoprotein A-I / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Protein Aggregates*
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Solutions


  • APOA1 protein, human
  • Amyloid
  • Apolipoprotein A-I
  • Peptides
  • Protein Aggregates
  • Solutions