Differences in the Binding of Copper(I) to α- and β-Synuclein
| Autor: | Gianni Valensin, Luigi Casella, Riccardo De Ricco, Daniela Valensin, Simone Dell'Acqua, Elena Gaggelli, Luigi Bubacco, Stefano Mangani |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Circular dichroism
Amyloid Molecular Sequence Data chemistry.chemical_element medicine.disease_cause Inorganic Chemistry Pathogenesis Methionine beta-Synuclein medicine Chemical Precipitation Humans Amino Acid Sequence Physical and Theoretical Chemistry Solid-Phase Synthesis Techniques Mutation Lysine Bioinorganic chemistry Cations Monovalent Copper Solutions chemistry Biochemistry alpha-Synuclein Peptides Homeostasis Oxidative stress Protein Binding |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|