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Hot spots in apolipoprotein A-II misfolding and amyloidosis in mice and men.

ABSTRACT: 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 ?-helical conformation to cross-?-sheet in amyloid, is unknown. We used 12 sequence-based prediction algorithms to identify two ten-residue segments in apoA-II that probably initiate ?-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 ?-aggregation.

SUBMITTER: Gursky O

PROVIDER: S-EPMC3979420 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Hot spots in apolipoprotein A-II misfolding and amyloidosis in mice and men.

Gursky Olga O

FEBS letters 20140220 6

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 α-helical conformation to cross-β-sheet in amyloid, is unknown. We used 12 sequence-based prediction algorithms to identify two ten-residue segments in apoA-II that probably initiate β-aggregation. Previous studies of apoA-II fragments experimentally v ...[more]

PMID: 24561203

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