Coordination of Ni(II) ions to a C-terminal fragment of Cap43 protein: an NMR study

ne of the research topics in our group is protein Cap 43, which seems directly related to the cellular response after nickel exposure, as well as to a number of cancers. The studies we carried out for several years started from a small peptide model of Cap 43 and were successively expanded to include a three-repeated monohistidinic decapeptide region in its C-terminal domain TRSRSHTSEG- TRSRSHTSEG-TRSRSHTSEG. Such a 30-aminoacid sequence was tested for Ni(II) coordination using NMR spectroscopy. At pH = 9.0 and for a ligand-to-metal molar ratio of 1:3 each 10-aminoacid fragment showed its ability to coordinate a single Ni(II) ion. The coordination involved an imidazole nitrogen from His residue, amidic nitrogens from His, Ser, and Arg in the plane, and an apical interaction with an oxygen atom from a Ser residue. A model for the structure of the complex was derived from the inter-residual ROEs recorded in 2D 1H-1H ROESY NMR spectra.