Coordination of Divalent Cations to a Multihistidinic Domain in Cap43 Protein

摘要

Multi-histidinic peptides have been investigated for Ni(II) and Cu(II) binding. We present spectroscopic evidencethat, at low pH and from sub-stoichiometric to stoichiometric amounts of metals, macrochelate and multi-histidinicNi(II) and Cu(II) complexes are formed; but, from neutral pH and above, both nickel and copper bind to individualhistidine residues. NMR, EPR, UV–Visible and UV–Visible CD spectroscopy were used to understand about thevariety of complexes obtained at low pHs, where amide deprotonation and coordination is unfavoured. A structuraltransition between two coordination geometries, as the pH is raised, was observed. From EPR a distortion fromplanarity has been evidenced for the Cu(II) multi-histidinic macrochelate systems, which may be relevant to biologicalactivity. The behaviour of our peptides was comparable to the pH-dependent effect on Cu(II) coordinationobserved in octapeptide repeat domain in prion proteins and in amyloid precursor peptides involved in Alzheimer'sdisease. Changes in pH and levels of metal affect coordination mode and can have implications for the affinity,folding and redox properties of proteins and peptide fragments.