title: Differences in the binding of copper(I) to α- and β-synuclein.
abstract: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the presence of abnormal α-synuclein (αS) deposits in the brain. Alterations in homeostasis and metal-induced oxidative stress may play a crucial role in the progression of αS amyloid assembly and pathogenesis of PD. Contrary to αS, β-synuclein (βS) is not involved in the PD etiology. However, it has been suggested that the βS/αS ratio is altered in PD, indicating that a correct balance of these two proteins is implicated in the inhibition of αS aggregation. αS and βS 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 βS and αS 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 βS and αS, respectively. These new insights into the bioinorganic chemistry of copper and synuclein proteins are a basis to understand the molecular mechanism by which βS might inhibit αS aggregation.
authors.affiliation: Department of Biotechnology, Chemistry, and Pharmacy, University of Siena , Via Aldo Moro 2, Siena, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: De Ricco
authors.forename: Daniela
authors.initials: D
authors.lastname: Valensin
authors.forename: Simone
authors.initials: S
authors.lastname: Dell'Acqua
authors.forename: Luigi
authors.initials: L
authors.lastname: Casella
authors.forename: Elena
authors.initials: E
authors.lastname: Gaggelli
authors.forename: Gianni
authors.initials: G
authors.lastname: Valensin
authors.forename: Luigi
authors.initials: L
authors.lastname: Bubacco
authors.forename: Stefano
authors.initials: S
authors.lastname: Mangani
mesh_terms: D000595:Amino Acid Sequence; D002414:Cations, Monovalent; D011232:Chemical Precipitation; D003300:Copper / Q000737:chemistry*; D006801:Humans; D008239:Lysine / Q000737:chemistry; D008715:Methionine / Q000737:chemistry; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D060327:Solid-Phase Synthesis Techniques; D012996:Solutions; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics; D051846:beta-Synuclein / Q000737:chemistry* / Q000235:genetics
chemical_list: D002414:Cations, Monovalent; D010455:Peptides; D012996:Solutions; D051844:alpha-Synuclein; D051846:beta-Synuclein; D003300:Copper; D008715:Methionine; D008239:Lysine