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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
- Gielnik, Maciej, Pietralik, Zuzanna, Zhukov, Igor, Szymańska, Aneta, Kwiatek, Wojciech M., Kozak, Maciej
- RSC advances 2019 v.9 no.39 pp. 22211-22219
- Fourier transform infrared spectroscopy, X-ray diffraction, amyloid, atomic force microscopy, cytotoxicity, dyes, humans, metal ions, peptides, prion diseases, prions, protein folding, transmission electron microscopy, zinc
- 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.