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PrP (58-93) peptide from unstructured N-terminal domain of human prion protein forms amyloid-like fibrillar structures in the presence of Zn2+ ions

机译:来自非结构化N-末端结构域的PRP(58-93)肽在Zn2 +离子存在下形成淀粉样蛋白样纤维状结构

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摘要

Many transition metal ions modulate the aggregation of different amyloid peptides. Substoichiometric zinc concentrations can inhibit aggregation, while an excess of zinc can accelerate the formation of cytotoxic fibrils. In this study, we report the fibrillization of the octarepeat domain to amyloid-like structures. Interestingly, this self-assembling process occurred only in the presence of Zn(ii) ions. The formed peptide aggregates are able to bind amyloid specific dyes thioflavin T and Congo red. Atomic force microscopy and transmission electron microscopy revealed the formation of long, fibrillar structures. X-ray diffraction and Fourier transform infrared spectroscopy studies of the formed assemblies confirmed the presence of cross-beta structure. Two-component analysis of synchrotron radiation SAXS data provided the evidence for a direct decrease in monomeric peptide species content and an increase in the fraction of aggregates as a function of Zn(ii) concentration. These results could shed light on Zn(ii) as a toxic agent and on the metal ion induced protein misfolding in prion diseases.
机译:许多过渡金属离子调节不同淀粉样蛋白肽的聚集。倒锌浓度可以抑制聚集,而过量的锌可以加速细胞毒性原纤维的形成。在这项研究中,我们将烯烷域域的原纤化报告给淀粉样蛋白状结构。有趣的是,这种自组装过程仅在Zn(II)离子的存在下发生。形成的肽聚集体能够将淀粉样蛋白特异性染料结合硫蛋白T和刚果红色。原子力显微镜和透射电子显微镜显示长,纤维状结构的形成。形成的组件的X射线衍射和傅里叶变换红外光谱研究证实了β结构的存在。同步辐射纱布的双组分分析提供了单体肽种类含量直接降低的证据,以及作为Zn(II)浓度的函数的聚集体级分的增加。这些结果可以在Zn(II)上作为有毒代理和金属离子诱导的朊病毒毒性蛋白质脱落。

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  • 来源
    《RSC Advances》 |2019年第39期|共9页
  • 作者单位

    Adam Mickiewicz Univ Fac Phys Dept Macromol Phys Uniwersytetu Poznanskiego 2 PL-61614 Poznan Poland;

    Adam Mickiewicz Univ Fac Phys Dept Macromol Phys Uniwersytetu Poznanskiego 2 PL-61614 Poznan Poland;

    Polish Acad Sci Inst Biochem &

    Biophys PL-02106 Warsaw Poland;

    Gdansk Univ Fac Chem Dept Biomed Chem PL-80308 Gdansk Poland;

    Polish Acad Sci Inst Nucl Phys PL-31342 Krakow Poland;

    Adam Mickiewicz Univ Fac Phys Dept Macromol Phys Uniwersytetu Poznanskiego 2 PL-61614 Poznan Poland;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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