Journal
FEBS LETTERS
Volume 588, Issue 6, Pages 845-850Publisher
WILEY
DOI: 10.1016/j.febslet.2014.01.066
Keywords
High-density lipoprotein; Amyloidogenic mutations; alpha-helix to beta-sheet conversion; Amphipathic alpha-helix; Lipid surface binding proteins
Funding
- National Institutes of Health [GM067260]
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ApoA-II is the second-major protein of high-density lipoproteins. C-terminal extension in human apoA-II or point substitutions in murine apoA-II cause amyloidosis. The molecular mechanism of apolipoprotein misfolding, from the native predominantly alpha-helical conformation to cross-beta-sheet in amyloid, is unknown. We used 12 sequence-based prediction algorithms to identify two tenresidue segments in apoA-II that probably initiate beta-aggregation. Previous studies of apoA-II fragments experimentally verify this prediction. Together, experimental and bioinformatics studies explain why the C-terminal extension in human apoA-II causes amyloidosis and why, unlike murine apoA-II, human apoA-II normally does not cause amyloidosis despite its unusually high sequence propensity for beta-aggregation. (C) 2014 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.
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