Nickel Binding to Cap43 protein

Cap43 has been reported to be specifically induced by nickel compounds in a variety of cell lines. Although the function of the Cap43 protein (MW 43,000) 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, for this reason it is named Cap43:Calciumprotein43,000. Cap43 protein is expressed at low levels in normal tissues however, in a variety of cancers, it is overexpressed in cancer cells. The high level of expression in cancerous status combined with the elevated stability of Cap43 protein makes it an excellent cancer marker.A possible way to better understand the molecular mechanisms implicated in toxicity and carcinogenicity of nickel compounds is to study the characteristics of the proteins expressed by the genes specifically induced by these carcinogens. 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 monohistidinic motif consisting of ten amino acids (TRSRSHTSEG) repeated three times in the C-terminus.We have analyzed, for Ni(II) binding, the 30-amino acid C-terminal sequence of the protein, TRSRSHTSEG-TRSRSHTSEGTRSRSHTSEG, by a combined pH-metric and spectroscopic (UV-VIS, CD, NMR) study.Our results support the existence of an interesting binding site for Ni(II) at the C-terminal domain of the Cap43 protein.