The opposite effects of Cu(II) and Fe(III) on the assembly of glucagon amyloid fibrils
The opposite effects of Cu(II) and Fe(III) on the assembly of glucagon amyloid fibrils
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DOI：
10.1039/c2ra20651j
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发表时间：
2012-05
期刊：
影响因子：
3.9
通讯作者：
Xingfei Zhou;Juhua Tan;Lifei Zheng;S. Pillai;Bin Li;Peng Xu;Bo Zhang;Yi Zhang
中科院分区：
文献类型：
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作者：
Xingfei Zhou;Juhua Tan;Lifei Zheng;S. Pillai;Bin Li;Peng Xu;Bo Zhang;Yi Zhang
一些过渡金属离子被认为是调节淀粉样多肽聚集的辅助因素，这被认为是调节多肽细胞毒性的关键因素。本文利用多种生物物理技术，探讨了铜(II)和铁(III)对胰升糖素多肽聚集/纤颤的影响。AFM分析表明，Cu(II)能促进胰升糖素多肽转化为淀粉样纤维，而Fe(III)则能显著抑制纤维的形成。值得注意的是，在较高的铜(II)浓度(200微米)下，球状集合体占主导地位，大量的纤维从球状核心伸出。然而，当Fe(III)浓度增加到100mU M以上时，只观察到几个纳米尺度的球形聚集体。此外，还发现与Cu(II)或Fe(III)共同孵育的胰高血糖素的FTIR和CD光谱与不加离子的情况明显不同。这些结果有力地表明，在胰升糖素的自发纤颤过程中，铜(II)和铁(III)可以显著改变聚集体的形态和二级结构。我们的研究可能有助于揭示金属离子如何调节胰升糖素多肽的淀粉样聚集性，并可能为未来的技术应用提供一种可控的淀粉样纳米结构合成手段。
A few transition metal ions are strongly implicated as co-factors in modulating the aggregation of amyloid peptides, which is believed to be a key factor in regulating the cytotoxicity of peptides. In this paper, we explored the effects of Cu(II) and Fe(III) on the aggregation/fibrillation of glucagon peptides using various biophysical techniques. AFM analysis demonstrated that Cu(II) could promote the conversion of glucagon peptides into amyloid fibrils, while the formation of fibrils was profoundly suppressed in the presence of Fe(III). Strikingly, at higher Cu(II) concentration (200 mu M), spherical assemblies were predominant with abundant fibrils protruding from spherical cores. However, only globular aggregates of several nanometers size were observed when the concentration of Fe(III) was increased beyond 100 mu M. In addition, it was also found that the FTIR and CD spectra of glucagon co-incubated with Cu(II) or Fe(III) remarkably differed from that in the absence of ions. These results strongly suggested that Cu(II) and Fe(III) could dramatically modify the morphologies as well as the secondary structures of aggregates during the spontaneous fibrillation of glucagon. Our study could shed light on how the metal ions regulate the amyloid aggregation of glucagon peptide, and might provide a controllable means for the synthesis of amyloid nanostructures for future technological applications.