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

Abstract

BackgroundElegant 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.MethodsNMR 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.ResultsThe 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.ConclusionsThe 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.

Reversible Conformational Change in the Plasmodium falciparum Circumsporozoite Protein Masks Its Adhesion Domains

“…3D), demonstrating the integrity of the individual proteins. The recent observation that Ca 2ϩ binds the CSP repeat region (37) leaves open the possibility that that there may be a role for Ca 2ϩ binding and the change in CSP conformation observed here.…”

Structure and mode of action of cyclic lipopeptide pseudofactin II with divalent metal ions

“…The conformational changes that facilitate ion binding and transport can be studied in considerable detail using molecular dynamics calculations [20], circular dichroism (CD) [21] and Xray crystallographic techniques [22], and such studies provide important insights on the mechanisms underlying ion binding and transport through membranes at the molecular level. Additionally, mass spectrometry (MS) techniques can also unravel metal binding interactions.…”