Nickel(II) binding to Cap43 protein fragments

Area of Science:

• Biochemistry
• Metalloprotein studies
• Protein structure and function

Background:

• Cap43 protein is induced by nickel compounds in human cells.
• A novel mono-histidinic motif, repeated thrice in the C-terminus, was identified.
• This motif is a potential nickel-binding site.

Purpose of the Study:

• To investigate the Ni(II) binding capabilities of Cap43 protein's C-terminal fragments.
• To characterize the metal-ligand complexes formed.
• To determine the coordination environment of Ni(II) ions.

Main Methods:

• Synthesis and analysis of two peptides (20- and 30-amino acid) representing the C-terminal motif.
• Combined pH-metric and spectroscopic (UV-visible, CD, NMR) studies.
• Analysis of Ni(II) binding stoichiometry and complex formation.

Main Results:

• Both peptides bind Ni(II) ions, with the 30-amino acid peptide binding up to three metal ions.
• Complexes formed include Ni(2)L (peptide 1) and NiL, Ni(2)L, Ni(3)L (peptide 2) at physiological pH.
• Coordination involves histidine imidazole nitrogen atoms, forming octahedral complexes at pH 8-9 and planar 4N complexes above pH 9.

Conclusions:

• The C-terminal domain of Cap43 protein possesses a significant Ni(II) binding site.
• The identified histidine-rich motif is crucial for nickel coordination.
• This finding contributes to understanding metalloprotein interactions and potential roles in nickel homeostasis or toxicity.