Cap43 has been reported to be specifically induced by nickel compounds in a variety of cell lines [1,2]. Although the function of the Cap43 protein is not clear, it does appear to be induced in response to an increase in intracellular concentration of Ca2+ , caused by nickel ion exposure in cultured human cells . Other protein like heat shock proteins, metallothioneins and acute phase reactant protein, are induced by nickel even if not specifically, like in the case of Cap43. It has been suggested that the function of these three families of proteins is in the detoxification and protection against oxidative stress induced by metals. For this reason we focused our attention to investigate the interaction ability of nickel to Cap43 protein. The peculiarity of protein Cap43 is its new mono-histidinic motif consisting of ten amino acids (TRSRSHTSEG) repeated three times in the C-terminus. We report 1D and 2D Tocsy and Roesy 1H-NMR studies of the binding of Ni(II) to the 30-aminoacid C-terminal sequence of the Cap43 protein, AcTRSRSHTSEG-TRSRSHTSEG-TRSRSHTSEG-Am. In order to test the coordination properties of individual single mono-histidinic motif, the analysis was performed in the different molar ratio 1:1, 2:1 and 3:1 for Ni(II) to ligand respectively. The diamagnetic shifts induced by Ni(II) were consistent with strong binding to a square-planar site formed by four nitrogen atoms derived from His (Nd1,NH) and the remaining two derived from NH of Ser and Arg, in the same coordination pattern and ability of Ni(II) to all three identical repeated region. Strong shifts in the aliphatic proton resonances of arginine suggest an active involvement of the its side-chain in the complex stability. Our results supports and complete the evidence, previous reported [3,4], of the existence of an interesting binding site for Ni(II) at the C-terminal domain of the Cap43 protein.
Nickel Binding to Cap43 protein / Zoroddu, Maria Antonietta; Peana, Massimiliano Francesco; Medici, Serenella; Kowalik Jankowska, Teresa; Kozlowski, Henryk. - (2005), pp. PP13-PP13. (Intervento presentato al convegno 8th FIGIPAS Meeting in Inorganic Chemistry tenutosi a Athens, Grecia nel 6-9 Luglio 2005).