Chelation of Ca²⁺ ions by a peptide from the repeat region of the Plasmodium falciparum circumsporozoite protein

Elegant efforts towards the determination of the structural tendencies of peptides derived from the Plasmodium falciparum circumsporozoite protein allowed the proposal of a left-handed helical conformation for this protein. The use of circular dichroism and Fourier-transformed infrared spectroscopy applied to various peptides derived from this protein, indicated that they bind Ca²⁺ ions in helical environments. The essential role of calcium in cell function and biological mechanisms is well known. It influences the development of several stages of the P. falciparum parasite. However, there is very little knowledge regarding calcium coordination to circumsporozoite proteins. In the present investigation the chelation of Ca²⁺ by the (NANPNVDP)₃NANP peptide, which contains the first seven 4-amino-acid blocks of the repeat region of the P. falciparum circumsporozoite protein, is tested with the use of circular dichroism and nuclear magnetic resonance spectroscopies. Spectroscopy-based solution conformations of the Ca-bound peptide are also determined. NMR spectroscopy and circular dichroism were used to test Ca²⁺ coordination by the peptide (NANPNVDP)3NANP. Solution conformations for the Ca-bound peptide were determined through molecular dynamics calculations. The NMR spectra collected for (NANPNVDP)₃NANP indicate that the signals generated by some of the amino acids located at its C-terminal end are shifted from their original positions upon Ca²⁺ addition. The solution conformations determined for the Ca-bound peptide indicate that the metal ion can be either six- or seven-coordinate. The investigation described herein strongly supports the coordination of Ca²⁺ ions to some of the amino acids located at the C-terminus of the peptide (NANPNVDP)₃NANP. The solution conformations determined for the Ca-bound congener of this peptide display many structural features associated to Ca-binding proteins.