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Coordination of Platinum to α‐Synuclein Inhibits Filamentous Aggregation in Solution
Author(s) -
Pan BinBin,
Yang Yin,
Liu HuiZhong,
Li YiHua,
Su XunCheng
Publication year - 2019
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900224
Subject(s) - circular dichroism , chemistry , platinum , biophysics , random coil , stereochemistry , protein aggregation , crystallography , lewy body , metal ions in aqueous solution , biochemistry , metal , organic chemistry , parkinson's disease , biology , disease , medicine , pathology , catalysis
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 Pt II ‐containing antitumor drug cisplatin suppresses filamentous aggregation of AS in solution. Pt II thus contrasts strongly with reported transition‐metal ions such as Mn II , Fe III , and Cu II , which accelerate AS aggregation. Interaction between Pt II and the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of Pt II 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 ⋅ Pt II 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.