Specificity in the Cu2+ interactions with prion protein fragments and related His-rich peptides from mammals to fishes

The prion proteins may play a critical role in copper homeostasis and the antioxidant activity in the brain. This review presents the state of art in the studies on Cu2+ prion systems. The proteins discussed are from different species from mammals to fishes. All proteins are His-rich and the research discussed clearly indicates the basic role of imidazole side chains and the adjacent amide nitrogen atoms in metal ion binding. Prions represent the family of proteins with new mode of Cu2+ binding which includes the amide nitrogen coordination. The multi-imidazole coordination is also likely and it can play a critical role in the antioxidant activity of the copper–prion complexes. The combination of the imidazole and amide nitrogen atoms to Cu2+ ions could also be relevant in histidine-rich peptide antibiotics including demegen. The impact of peptide sequence and His positions on copper binding ability is also discussed

Copper, iron, and zinc ions homeostasis and their role in neurodegenerative disorders (metal uptake, transport, distribution and regulation)

Metal ions, especially with high chemical activity (e.g. redox-active Cu and Fe) must be carefully managed in biological systems. The “uncontrolled” activity, e.g. catalysis of Fenton-like reactions by ions like Cu(I) or Fe(II), is so damaging for the biological milieu that right from their entry, metal ions need to be strictly controlled until they arrive at their storage site. This chaperoning occurs usually by proteins which are involved in transport, delivery and distribution processes. In this reviewsome aspects of the metal homeostasis for major metal ions (Cu, Fe, and Zn) are presented. The impact of these metals on some disorders are also discussed

THE UNUSUAL STABILIZATION OF THE Ni2+ AND Cu2+ COMPLEXES WITH NSFRY

The binding mode provided by an unprotected peptide with non-coordinating side-chains is simple and well understood. However, when particular residues are inserted into the peptide sequence, they can have a significant impact on the stability of the formed complexes. The presence of non-bonding side chains of amino acids close to the metal binding centre in the peptide/protein can provide special interactions which result in increasing the stabilization of the formed species. Moreover, these interactions can play a crucial role in generating particular protein structures and in influencing biological activity. In the present paper it is shown how peptides with no specific predisposition for metal binding, like ANF peptides, can form metal complexes with a very high thermodynamic stability. For better understanding this peculiar behavior, a combined pH-metric and spectroscopic method was used to determine the stability and the solution structure of Cu2+ and Ni2+ complexes with NSFRY-NH2 (ANF peptide) and a series of analogue peptides. All obtained data support the hypothesis that the complex-formation process is very similar for both metal ions and all the ligands, involving some intramolecular interactions among the different side chains. The two-dimensional NMR analysis of nickel complexes showed the occurrence of many inter-residue correlations and suggested the presence a direct interaction between the d electrons of the metal ion and the π-ring system of the aromatic side-chains of the ligand