Phosphorylation Impacts Cu(II) Binding by ATCUN Motifs

Area of Science:

• Biochemistry
• Metalloprotein Chemistry
• Post-Translational Modifications

Background:

• Amino terminal Cu(II) and Ni(II) binding (ATCUN) motifs are known for strong metal ion chelation.
• The influence of phosphorylation on metal binding by these motifs remains largely unexplored.

Purpose of the Study:

• To investigate the effect of phosphorylation on Cu(II) complexation by ATCUN motifs.
• To compare Cu(II) binding affinities of phosphorylated and unphosphorylated peptides from human proteins.

Main Methods:

• Spectroscopic methods were employed to determine copper(II) dissociation constants.
• Comparative analysis of peptides derived from human histatin-1 and human serum albumin.

Main Results:

• Phosphorylation was observed to markedly weaken Cu(II) binding to the studied peptides.
• Dissociation constants revealed a significant reduction in metal ion affinity upon phosphorylation.

Conclusions:

• Phosphorylation emerges as a critical regulatory mechanism influencing metal ion binding.
• These findings highlight the biological relevance of post-translational modifications in modulating metalloprotein function.