PROBING OF Cu2+ IONS BINDING TO Aβ(5−16) PEPTIDE USING ITC MEASUREMENTS AND MD SIMULATIONS

Abstract

It is shown that probably three residues: His6, His14 and His16 in the original sequence Aβ₍₁₋₄₂₎ serve as metal-binding sites for Cu²⁺ ions. On the other hand, there is a possibility that only one of them plays a crucial role in the formation of the {Aβ₍₁₋₄₂₎ --Cu²⁺} complex. The isothermal titration calorimetry (ITC) measurements supported by molecular dynamic simulation (MD) with the NMR derived restrains were used to investigate the interactions of Cu²⁺ with Aβ₍₅₋₁₆₎, a fragment of the Aβ₍₁₋₄₂₎ protein, with the following sequence: Ac--Arg--His--Asp--Ser--Gly--Tyr--Glu--Val--His--His--Gln--Lys--NH2, termed HZ1. The conditional thermodynamic parameters suggest that the formation of the Cu²⁺--HZ1 complex is both an enthalpy and entropy driven process under the experimental conditions. The studies presented here (after comparison with our previous results) show that the affinity of peptides to copper metal ions depends on two factors: the primary structure (amino acid composition) and the shape of the peptide conformation adopted.