Exploring the Structural Details of Cu(I) Binding to r-Synuclein by NMR Spectroscopy

Abstract: The aggregation of R-synuclein (AS) is selectively enhanced by copper in vitro, and the interaction is proposed to play a potential role in vivo. In this work, we report the structural, residue-specific characterization of Cu(I) binding to AS and demonstrate that the protein is able to bind Cu(I) with relatively high affinity in a coordination environment that involves the participation of Met1 and Met5 residues. This knowledge is a key to understanding the structural-aggregation basis of the copper-catalyzed oxidation of AS. The aggregation of R-synuclein (AS) is a critical step in the etiology of Parkinson’s disease (PD).1 Protein-metal interactions play an important role in AS aggregation and might represent the link between the pathological processes of protein aggregation, oxidative damage, and neuronal cell loss. As reported for the A peptide and the prion protein, AS is also highly susceptible t