Title
Heparin promotes fibril formation by the N‐terminal fragment of amyloidogenic apolipoprotein A‐I
Author
Shiho Mikawa, Chiharu Mizuguchi, Kazuchika Nishitsuji, Teruhiko Baba, Akira Shigenaga, Toshinori Shimanouchi, Naomi Sakashita, Akira Otaka, Kenichi Akaji, Hiroyuki Saito
Year
2016
Journal
FEBS Letters
Abstract
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.
Instrument
J-1500
Keywords
Circular dichroism, Secondary structure, Aggregation, Chemical stability, Biochemistry