Interaction of histone H2B (fragment 63–93) with Ni(ii). An NMR study

Abstract

The behaviour of the 31 mer peptide (Ac-NSFVNDIFERIAG₁₃EASRL₁₈A₁₉H₂₀YNKRS₂₅TITSRE-NH₂), modelling the histone-fold domain (63 to 93 residues) of H2B, towards Ni(II) was investigated by multidimensional NMR spectroscopy (1D, 2D TOCSY, NOESY and ¹³C-HSQC). The coordination involved the imidazole of His20 and three amide nitrogens of His20, Ala19 and Leu18, similar to the one shown by the hexapeptide LAHYNK contained in the 31 mer peptide. The solution structure of the Ni(II) complex with the tridecapeptide comprising histone's H2B 75–87 residues, was elucidated from the NOE cross correlations observed in the 2D-NOESY spectrum. A severe change in the peptide's conformation was observed, passing from a partially helical to a well-defined ordered structure around the metal ion. A remarkable structural feature is the position of the aromatic ring of Tyr21 below the coordination plane. This and the hydrophobic fence created by Leu18 and Ala19, together with the position of Arg17 and Arg24 side chains seem to be relevant to the complex stability. We believe that these structural modifications may be physiologically important in the mechanism of nickel induced carcinogenesis.