Gielnik Maciej, Pietralik Zuzanna, Zhukov Igor, Szymańska Aneta, Kwiatek Wojciech M, Kozak Maciej
Department of Macromolecular Physics, Faculty of Physics, Adam Mickiewicz University Uniwersytetu Poznańskiego 2 PL 61-614 Poznań Poland
Institute of Biochemistry and Biophysics, Polish Academy of Sciences PL 02-106 Warszawa Poland.
RSC Adv. 2019 Jul 17;9(39):22211-22219. doi: 10.1039/c9ra01510h.
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-β 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.
许多过渡金属离子可调节不同淀粉样肽的聚集。亚化学计量的锌浓度可抑制聚集，而过量的锌则可加速细胞毒性纤维的形成。在本研究中，我们报道了八肽重复结构域形成淀粉样结构的纤维化过程。有趣的是，这种自组装过程仅在Zn(ii)离子存在时发生。形成的肽聚集体能够结合淀粉样特异性染料硫黄素T和刚果红。原子力显微镜和透射电子显微镜揭示了长纤维状结构的形成。对形成的组装体进行的X射线衍射和傅里叶变换红外光谱研究证实了交叉β结构的存在。同步辐射SAXS数据的两组分分析提供了证据，表明单体肽种类含量随Zn(ii)浓度的增加而直接降低，聚集体比例增加。这些结果可能有助于阐明Zn(ii)作为一种有毒物质以及金属离子诱导的朊病毒疾病中的蛋白质错误折叠。
