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 journalLetter

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 languageEnglish
Pages (from-to)3492-3500
Number of pages9
JournalFEBS Letters
Volume590
Issue number20
DOIs
Publication statusPublished - Oct 1 2016

Fingerprint

Apolipoprotein A-I
Glycosaminoglycans
Heparin
Amyloidogenic Proteins
Peptide Fragments
Amyloid Plaques
Amyloid
Elongation
Deposits

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., ... 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 journalLetter

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, vol. 590, no. 20, pp. 3492-3500. https://doi.org/10.1002/1873-3468.12426
Mikawa, Shiho ; Mizuguchi, Chiharu ; Nishitsuji, Kazuchika ; Baba, Teruhiko ; Shigenaga, Akira ; Shimanouchi, Toshinori ; Sakashita, Naomi ; Otaka, Akira ; Akaji, Kenichi ; Saito, Hiroyuki. / Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I. In: FEBS Letters. 2016 ; Vol. 590, No. 20. pp. 3492-3500.
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