Coordination of Platinum to α‐Synuclein Inhibits Filamentous Aggregation in Solution
| Autor: | Hui-Zhong Liu, Yi-Hua Li, Xun-Cheng Su, Yin Yang, Bin-Bin Pan |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Circular dichroism
010405 organic chemistry Chemistry Metal ions in aqueous solution Organic Chemistry Antineoplastic Agents Nuclear magnetic resonance spectroscopy Protein aggregation 010402 general chemistry 01 natural sciences Biochemistry Random coil 0104 chemical sciences Solutions Protein Aggregates alpha-Synuclein Side chain Biophysics Synuclein Molecular Medicine Cisplatin Molecular Biology Histidine Platinum |
| Zdroj: | ChemBioChem. 20:1953-1958 |
| ISSN: | 1439-7633 1439-4227 |
| DOI: | 10.1002/cbic.201900224 |
| Popis: | Accumulation of filamentous aggregates of α-synuclein (AS) in Lewy bodies and neurites is characteristic of neurodegenerative diseases such as Parkinson's disease. Inhibition of AS fibrillation is helpful for understanding of AS aggregate structure and for developing chemical therapies. Herein, we report that the PtII -containing antitumor drug cisplatin suppresses filamentous aggregation of AS in solution. PtII thus contrasts strongly with reported transition-metal ions such as MnII , FeIII , and CuII , which accelerate AS aggregation. Interaction between PtII and the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of PtII to AS did not change the protein's overall random coil structure, as indicated by solution-state two-dimensional NMR and circular dichroism spectroscopy; and a solution of the AS⋅PtII complex remained free of filamentous aggregates. Our results constitute interesting new information about the biological chemistry of metal ions in Parkinson's disease and might open new lines of research into the suppression of filamentous aggregation. |
| Databáze: | OpenAIRE |
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