Mikawa Shiho, Mizuguchi Chiharu, Nishitsuji Kazuchika, Baba Teruhiko, Shigenaga Akira, Shimanouchi Toshinori, Sakashita Naomi, Otaka Akira, Akaji Kenichi, Saito Hiroyuki
Department of Biophysical Chemistry, Kyoto Pharmaceutical University, Japan.
Institute of Biomedical Sciences, Graduate School of Pharmaceutical Sciences, Tokushima University, Japan.
FEBS Lett. 2016 Oct;590(20):3492-3500. doi: 10.1002/1873-3468.12426. Epub 2016 Oct 4.
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.
已知糖胺聚糖与各种淀粉样蛋白的细胞外淀粉样沉积物有关。在本研究中，我们发现糖胺聚糖肝素极大地加速了人载脂蛋白A-I（apoA-I）N端1-83片段在纤维形成过程中的延伸步骤，尤其是在淀粉样变的W50R变体中。使用片段肽，我们证明肝素显著促进了跨越44-65位残基的高度淀粉样变区域的β转变和纤维形成，并与W50R变体形成的纤维共定位。这些结果表明糖胺聚糖在淀粉样变apoA-I变体纤维形成中可能发挥的作用。
