Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I

Shiho Mikawa; Chiharu Mizuguchi; Kazuchika Nishitsuji; Teruhiko Baba; Akira Shigenaga; Toshinori Shimanouchi; Naomi Sakashita; Akira Otaka; Kenichi Akaji; Hiroyuki Saito

doi:10.1002/1873-3468.12426

Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I

Shiho Mikawa, Chiharu Mizuguchi, Kazuchika Nishitsuji, Teruhiko Baba, Akira Shigenaga, Toshinori Shimanouchi, Naomi Sakashita, Akira Otaka, Kenichi Akaji, Hiroyuki Saito

Research output: Contribution to journal › Letter

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	3492-3500
Number of pages	9
Journal	FEBS Letters
Volume	590
Issue number	20
DOIs	https://doi.org/10.1002/1873-3468.12426
Publication status	Published - Oct 1 2016

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Keywords

amyloid
apolipoprotein A-I
heparin

ASJC Scopus subject areas

Structural Biology
Biophysics
Biochemistry
Molecular Biology
Genetics
Cell Biology

Cite this

Mikawa, S., Mizuguchi, C., Nishitsuji, K., Baba, T., Shigenaga, A., Shimanouchi, T., Sakashita, N., Otaka, A., Akaji, K., & Saito, H. (2016). Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I. FEBS Letters, 590(20), 3492-3500. https://doi.org/10.1002/1873-3468.12426

Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I. / Mikawa, Shiho; Mizuguchi, Chiharu; Nishitsuji, Kazuchika; Baba, Teruhiko; Shigenaga, Akira; Shimanouchi, Toshinori; Sakashita, Naomi; Otaka, Akira; Akaji, Kenichi; Saito, Hiroyuki.

In: FEBS Letters, Vol. 590, No. 20, 01.10.2016, p. 3492-3500.

Research output: Contribution to journal › Letter

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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.",

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AU - Shigenaga, Akira

AU - Shimanouchi, Toshinori

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AU - Otaka, Akira

AU - Akaji, Kenichi

AU - Saito, Hiroyuki

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AB - 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.

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10.1002/1873-3468.12426