Coordination of Cu2+and Ni2+ with the histone model peptide of H2B N-terminal tail (1-31 residues): A spectroscopic study

Abstract

The interaction of Cu²⁺ and Ni²⁺ with the N-terminal tail of histone H2B, the 31 amino acid peptide H2B_1-31 (Ac–PEPAKSAPAPKKG₁₃SKKAVTKAQKKD₂₅GKKRKR–NH₂), studied by various spectroscopic techniques (UV/Vis, CD, EPR and NMR) are described. The results showed the formation of Cu²⁺-H2B_1-31 complexes above pH 7.3 most probably through the β-carboxylate group of D25. With the increase of the pH, a mixture of 3 N and 4 N species presenting {2N⁻, CO, εNH₂} and {2N⁻, OH₂, εNH₂}{εNH₂} coordination modes, respectively is formed, while at highly basic solutions the binding of an additional amide donor is suggested. NMR spectroscopy supported by CD spectroscopy indicated that Ni²⁺ coordination takes place most likely through Q22-K23-K24-D25 peptide fragment. Direct coordination to Ni²⁺, in a {4N⁻} coordination mode, with a severe conformation change in all residues from G13 to G26 was observed. Cu²⁺ and Ni²⁺ binding to the N-terminal tail of H2B causes a severe conformational change that might interfere with histone post-translational modifications, possibly leading to epigenetic changes.