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

Abstract

Zinc ions modulate the aggregation of PrP (58–93) amyloid peptide.

Metals in ALS TDP-43 Pathology

“…Later, a Zn-binding site in the RRM2 domain has been described, likely involving the negatively charged glutamate E261 and the two histidines H256 and H264 [130]. Similar results have been observed for the binding of Zn ions to histidine residues in PrP [141,142]. However, binding of a single Zn ion to the Aβ peptide involved in AD, mainly via histidines, promoted disordered aggregation and retarded formation of regular amyloid fibrils [61,143,144].…”

“…Aggregation of TDP-43 has been observed in the majority of all studied ALS cases (Figure 1) [9,31,32]. Protein aggregation is influenced by several physico-chemical variables, such as changes in pH and temperature [59], interactions with other proteins [63,[136][137][138][139], and by binding of metal ions to specific metal-binding regions [52,[60][61][62]125,140,141]. Six metals with known neurotoxic properties have been studied in relation to TDP-43 so far, i.e., Pb, Hg, Zn, Fe, Cu and Mn (Table 1).…”

The engineered peptide construct NCAM1-Aβ inhibits aggregation of the human prion protein (PrP)

“…Many of these proteins and peptides may co-aggregate or at least influence each other's aggregation (Luo et al, 2016(Luo et al, , 2017Ren et al, 2019;Wallin et al, 2018). Factors that modulate the aggregation of one of these proteins, such as small molecules, potential drug compounds, lipids, and metal ions, can often modulate also the aggregation processes of other proteins in this family (Ambadi Thody et al, 2018;Chemerovski-Glikman et al, 2016;Gielnik et al, 2019;Owen et al, 2019;Richman et al, 2013;Robinson and Pinheiro, 2010;Wallin et al, 2017;Wärmländer et al, 2013;Wärmländer et al, 2019;Österlund et al, 2018). This suggests that the underlying mechanisms may be the same in prion and amyloid diseases (Jaunmuktane and Brandner, 2019;Jucker and Walker, 2018;Miller, 2009).…”

The Prion Protein Octarepeat Domain Forms Transient β-sheet Structures Upon Residue-Specific Cu(II) and Zn(II) Binding

“…Previous studies have suggested that Cu(II) and Zn(II) ions may inhibit in vitro conversion of PrP C to PrP Sc by formation of nonamyloid aggregates 92 . However, we have previously reported that after addition of four molar equivalents of Zn(II) ions, the OR peptide forms structured fibrils that bind the amyloid-specific dyes Thioflavin T and Congo Red, and which display the cross-β structure typical for amyloid material 50 . Thus, the OR peptide incubated with an excess of Cu(II) ions may also form amyloid aggregates.…”

“…We have recently shown that the isolated OR region (i.e., an OR peptide) upon interaction with Zn(II) ions forms fibrillar cross-β structures that bind thioflavin T and Congo Red, and which possess all the characteristic features of amyloid material 50 . This indicates that metal ions can directly induce a transition of PrP C into the amyloid state.…”