Coordination of Platinum to alpha-Synuclein Inhibits Filamentous Aggregation in Solution.
Coordination of Platinum to alpha-Synuclein Inhibits Filamentous Aggregation in Solution.
复制标题
铂与 α-突触核蛋白的配位可抑制溶液中的丝状聚集。
DOI：
10.1002/cbic.201900224
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发表时间：
2019
期刊：
影响因子：
3.2
通讯作者：
Su Xun Cheng
中科院分区：
文献类型：
--
作者：
Pan Bin Bin;Yang Yin;Liu Hui Zhong;Li Yi Hua;Su Xun Cheng
α-突触核蛋白（AS）的丝状聚集体在路易体和神经突中的积累是神经退行性疾病（如帕金森病）的特征。抑制AS纤维化有助于理解AS聚集体结构和开发化学治疗方法。在这里，我们报告说，铂-含抗肿瘤药物顺铂抑制丝状聚集AS在溶液中。PtII因此与报道的过渡金属离子如MnII，FeIII和CuII形成强烈对比，这些离子加速AS聚集。PtII与甲硫氨酸和组氨酸残基侧链的相互作用是抑制AS纤维化的必要条件。溶液态二维NMR和圆二色性光谱表明，PtII与AS的结合并没有改变蛋白质的整体无规卷曲结构; AS-PtII复合物的溶液仍然没有丝状聚集体。我们的研究结果构成了有趣的新信息，在帕金森氏病的金属离子的生物化学，并可能打开新的研究线抑制丝状聚集。
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. PtIIthus contrasts strongly with reported transition‐metal ions such as MnII, FeIII, and CuII, which accelerate AS aggregation. Interaction between PtIIand the side chains of methionine and histidine residues was essential for inhibition of AS fibrillation. Binding of PtIIto 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⋅PtIIcomplex 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.