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Heparin promotes fibril formation by the N‐terminal fragment of amyloidogenic apolipoprotein A‐I
Author(s) -
Mikawa Shiho,
Mizuguchi Chiharu,
Nishitsuji Kazuchika,
Baba Teruhiko,
Shigenaga Akira,
Shimanouchi Toshinori,
Sakashita Naomi,
Otaka Akira,
Akaji Kenichi,
Saito Hiroyuki
Publication year - 2016
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 - 10.1002/1873-3468.12426
Subject(s) - fibril , glycosaminoglycan , chemistry , heparin , amyloid (mycology) , biochemistry , amyloid fibril , apolipoprotein b , biophysics , amyloid β , biology , medicine , inorganic chemistry , disease , pathology , cholesterol
Glycosaminoglycans are known to be associated with extracellular amyloid deposits of various amyloidogenic proteins. In this study, we found that the glycosaminoglycan heparin greatly accelerates the elongation step in fibril formation by the N‐terminal 1–83 fragment of human apolipoprotein A‐I (apoA‐I), especially in the amyloidogenic W50R variant. Using fragment peptides, we demonstrate that heparin significantly promotes β‐transition and fibril formation of the highly amyloidogenic region spanning residues 44–65 and colocalizes with fibrils formed by the W50R variant. These results suggest the possible role of glycosaminoglycans in fibril formation by amyloidogenic apoA‐I variants.