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Hot spots in apolipoprotein A‐II misfolding and amyloidosis in mice and men
Author(s) -
Gursky Olga
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.01.066
Subject(s) - amyloidosis , amyloid fibril , apolipoprotein b , chemistry , medicine , biochemistry , cholesterol , amyloid β , disease
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 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 β‐aggregation.