Coordination of Divalent Cations to a Multihistidinic Domain in Cap43 Protein

Multi-histidinic peptides have been investigated for Ni(II) and Cu(II) binding. We present spectroscopic evidence that, at low pH and from sub-stoichiometric to stoichiometric amounts of metals, macrochelate and multi-histidinic Ni(II) and Cu(II) complexes are formed; but, from neutral pH and above, both nickel and copper bind to individual histidine residues. NMR, EPR, UV-Visible and UV-Visible CD spectroscopy were used to understand about the variety of complexes obtained at low pHs, where amide deprotonation and coordination is unfavoured. A structural transition between two coordination geometries, as the pH is raised, was observed. From EPR a distortion from planarity has been evidenced for the Cu(II) multi-histidinic macrochelate systems, which may be relevant to biological activity. The behaviour of our peptides was comparable to the pH-dependent effect on Cu(II) coordination observed in octapeptide repeat domain in prion proteins and in amyloid precursor peptides involved in Alzheimer's disease. 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.