Differences in the binding of copper(I) to \u3b1- and \u3b2-synuclein.

Parkinsons disease (PD) is a neurodegenerative disorder characterized by the presence of abnormal \u3b1-synuclein (\u3b1S) deposits in the brain. Alterations in homeostasis and metal-induced oxidative stress may play a crucial role in the progression of \u3b1S amyloid assembly and pathogenesis of PD. Contrary to \u3b1S, \u3b2-synuclein (\u3b2S) is not involved in the PD etiology. However, it has been suggested that the \u3b2S/\u3b1S ratio is altered in PD, indicating that a correct balance of these two proteins is implicated in the inhibition of \u3b1S aggregation. \u3b1S and \u3b2S share similar abilities to coordinate Cu(II). In this study, we investigated and compared the interaction of Cu(I) with the N-terminal portion of \u3b2S and \u3b1S by means of NMR, circular dichroism, and X-ray absorption spectroscopies. Our data show the importance of M10K mutation, which induces different Cu(I) chemical environments. Coordination modes 3S1O and 2S2O were identified for \u3b2S and \u3b1S, respectively. These new insights into the bioinorganic chemistry of copper and synuclein proteins are a basis to understand the molecular mechanism by which \u3b2S might inhibit \u3b1S aggregation