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 binding. The unique structure of the N-terminal tail of histone H4 contains sites for post-translational modification close to a histidine residue capable of anchoring binding sites for metal ions. We have analyzed as a minimal model for the H4 tail, the blocked peptide CH(3)CO-AKRHRK-CONH(2) for nickel and copper binding. Ultraviolet-visible, circular dichroism, electron paramagnetic resonance and nuclear magnetic resonance spectroscopic analysis showed that histidine acts as an anchoring metal binding site. A 1N complex is formed 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-spin octahedral resulted in a 4N low-spin planar Ni(II) complex. The stability constants of the Cu(II) (3N, 4N) and Ni(II) (4N) complexes with the peptide 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 alphaproton region in the 1H NMR spectrum of the 4N Ni-complex showed that the conformation of the peptide had been dramatically affected following Ni(II) complexation.
Zoroddu
M A
MA
Department of Chemistry, University of Sassari, Italy. zoroddu@ssmain.uniss.it
Kowalik-Jankowska
T
T
Kozlowski
H
H
Molinari
H
H
Salnikow
K
K
Broday
L
L
Costa
M
M
D000595:Amino Acid Sequence; D001665:Binding Sites; D003300:Copper / Q000737:chemistry*; D006657:Histones / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009532:Nickel / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry; D010446:Peptide Fragments / Q000737:chemistry; D011199:Potentiometry
D006657:Histones; D009942:Organometallic Compounds; D010446:Peptide Fragments; D003300:Copper; D009532:Nickel