Institute of Health Biosciences and Graduate School of Pharmaceutical Sciences, The University of Tokushima, 1-78-1 Shomachi, Tokushima 770-8505, Japan.
Department of Medicinal Chemistry, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
FEBS Lett. 2014 Jan 31;588(3):389-94. doi: 10.1016/j.febslet.2013.11.031. Epub 2013 Dec 5.
The N-terminal 1-83 residues of apolipoprotein A-I (apoA-I) have a strong propensity to form amyloid fibrils, in which the 46-59 segment was reported to aggregate to form amyloid-like fibrils. In this study, we demonstrated that a fragment peptide comprising the extreme N-terminal 1-43 residues strongly forms amyloid fibrils with a transition to β-sheet-rich structure, and that the G26R point mutation enhances the fibril formation of this segment. Our results suggest that in addition to the 46-59 segment, the extreme N-terminal region plays a crucial role in the development of amyloid fibrils by the N-terminal fragment of amyloidogenic apoA-I variants.
载脂蛋白 A-I（apoA-I）的 N 端 1-83 残基具有很强的形成淀粉样纤维的倾向，其中报道 46-59 片段聚集形成类似淀粉样纤维。在这项研究中，我们证明了包含极端 N 端 1-43 残基的片段肽强烈形成富含β-折叠结构的淀粉样纤维，并且 G26R 点突变增强了该片段的纤维形成。我们的结果表明，除了 46-59 片段外，淀粉样纤维的形成由淀粉样蛋白 apoA-I 变体的 N 端片段，极端 N 端区域也起着至关重要的作用。
