Interaction of Ni(II) and Cu(II) with a metal binding sequence of histone H4: AKRHRK, a model of the H4 tail

Chromatin proteins are believed to represent reactive sites for nickel bind ing. The unique structure of the N-terminal tail of histone H4 contains sit es for post-translational modification close to a histidine residue capable of anchoring binding sites for metal ions. We have analyzed as a minimal m odel for the H4 tail, the blocked peptide CH3CO-AKRHRK-CONH2 for nickel and copper binding. Ultraviolet-visible. circular dichroism, electron paramagn etic resonance and nuclear magnetic resonance spectroscopic analysis showed that histidine acts as an anchoring metal binding site. A 1N complex is fo rmed between pH = 5-7 and 4-6 for Ni(II) and Cu(II), respectively, while at a higher pH a series of 4N complexes are formed. Above pH 8, the 2N high-s pin octahedral resulted in a 4N low-spin planar Ni(II) complex. The stabili ty constants of the Cu(II) (3N. 4N) and Ni(II) (4N) complexes with the pept ide model of the H4 were distinctly higher than those for a similar blocked peptide with a histidine in the fourth position. Significant shifts in the alpha proton region in the H-1 NMR spectrum of the 4N Ni-complex showed th at the conformation of the peptide had been dramatically affected following NI(II) complexation. (C) 2000 Elsevier Science B.V. All rights reserved.