Cu2 binding modes of recombinant α-synuclein - Insights from EPR spectroscopy

Abstract

The interaction of the small (140 amino acid) protein, α-synuclein (αS), with Cu2+ has been proposed to play a role in Parkinson's disease (PD). While some insight from truncated model complexes has been gained, the nature of the corresponding Cu2+ binding modes in the full length protein remains comparatively less well characterized. This work examined the Cu2+ binding of recombinant human αS using Electron Paramagnetic Resonance (EPR) spectroscopy. Wild type (wt) αS was shown to bind stoichiometric Cu2+ via two N-terminal binding modes at physiological pH. An H50N mutation isolated one binding mode, whose g II, AII, and metal-ligand hyperfine parameters correlated well with a {NH2, N-, β-C..