Phosphorylation of an alpha-synuclein peptide fragment enhances metal binding.

By using Tb3+ as a luminescent probe, we demonstrate that the phosphorylation state of a 14-residue peptide fragment of alpha-synuclein, a protein implicated in Parkinson's Disease, dramatically affects the metal ion affinity of the peptide. Whereas the unphosphorylated peptide and its phosphoserine analogue show weak Tb3+ binding, its phosphotyrosine analogue shows tight 1:1 binding as well as 2:1 and 3:1 Tb:peptide adducts. Our data suggest that the phosphorylated amino acid must be appropriately positioned among additional ligating residues to establish this phosphorylation-dependent metal binding.