Multidimensional NMR spectroscopy is a useful tool for the calculation of structures or structural models of metal-peptide complexes in solution. We applied bidimensional
NMR techniques to study the interactions of Ni(II) ions with a 30-aminoacid peptide, a fragment of the C-terminal tail of Cap 43 protein. This protein is strictly connected to nickel exposure in cells, since it seems to be specifically expressed as a response to the presence of this metal in the cellular medium and it is also related to cancer development; an abnormal level of Cap43 protein has been detected in a number of tumour tissues. The striking feature of Cap 43 is a three-repeated decapeptide
sequence at its C-terminus; each 10-aminoacid fragment (TRSRSHTSEG) bearing a histidinic residue, which has been indicated as an anchoring site for metal binding in
numerous cases. We previously reported that each fragment is able to coordinate a Ni(II) ion in a very effective way. Structure calculations for the peptide-metal complex were performed for a single monohistidinic fragment on the basis of the ROE crosscorrelations observed in the 2D 1H-1H ROESY spectra at pH = 10. The metal complex involves an imidazolic nitrogen of histidine residue, three amidic nitrogens of the backbone and an oxygen atom from a deprotonated serine residue which takes part to the formation of a square pyramidal structure.
The structural model calculated allowed us a better understanding of the features of nickel coordination with the C-terminal region of Cap43 protein
