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 | |
| 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
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
}
TY - JOUR
T1 - Heparin promotes fibril formation by the N-terminal fragment of amyloidogenic apolipoprotein A-I
AU - Mikawa, Shiho
AU - Mizuguchi, Chiharu
AU - Nishitsuji, Kazuchika
AU - Baba, Teruhiko
AU - Shigenaga, Akira
AU - Shimanouchi, Toshinori
AU - Sakashita, Naomi
AU - Otaka, Akira
AU - Akaji, Kenichi
AU - Saito, Hiroyuki
PY - 2016/10/1
Y1 - 2016/10/1
N2 - 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.
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.
KW - amyloid
KW - apolipoprotein A-I
KW - heparin
UR - http://www.scopus.com/inward/record.url?scp=84992473194&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84992473194&partnerID=8YFLogxK
U2 - 10.1002/1873-3468.12426
DO - 10.1002/1873-3468.12426
M3 - Letter
C2 - 27654470
AN - SCOPUS:84992473194
VL - 590
SP - 3492
EP - 3500
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 20
ER -