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
N1 - Funding Information:
Transmission electron microscopy observations were performed by Drs. K. Yan and K. Hirose (EM team, Tsukuba Innovation Arena, AIST, Tsukuba), partly supported by IBEC Innovation Platform, AIST. This work was partly supported by JSPS KAKENHI Grant Number JP25293006 (to H.S.).
Publisher Copyright:
© 2016 Federation of European Biochemical Societies
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
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
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U2 - 10.1002/1873-3468.12426
DO - 10.1002/1873-3468.12426
M3 - Article
C2 - 27654470
AN - SCOPUS:84992473194
VL - 590
SP - 3492
EP - 3500
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 20
ER -