α-Synuclein (α-Syn) is an intrinsically disordered protein which self-assembles into highly organized β-sheet structures that accumulate in plaques in brains of Parkinson’s disease patients. Oxidative stress influences α-Syn structure and self-assembly; however, the basis for this remains unclear. Here we characterize the chemical and physical effects of mild oxidation on monomeric α-Syn and its aggregation. Using a combination of biophysical methods, small-angle X-ray scattering, and native ion mobility mass spectrometry, we find that oxidation leads to formation of intramolecular dityrosine cross-linkages and a compaction of the α-Syn monomer by a factor of √2. Oxidation-induced compaction is shown to inhibit ordered self-assembly and amyloid formation by steric hindrance, suggesting an important role of mild oxidation in preventing amyloid formation.

中文翻译：

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二酪氨酸介导的α-突触核蛋白原纤维化抑制的结构基础

α-突触核蛋白 (α-Syn) 是一种本质上无序的蛋白质，可自组装成高度有序的 β 折叠结构，这些结构在帕金森病患者大脑的斑块中积聚。氧化应激影响 α-Syn 结构和自组装；然而，其依据仍不清楚。在这里，我们描述了轻度氧化对单体 α-Syn 及其聚集的化学和物理影响。使用生物物理方法、小角 X 射线散射和天然离子迁移质谱法的组合，我们发现氧化导致分子内二酪氨酸交联的形成和 α-Syn 单体的压实 √2 . 氧化诱导的压实显示通过空间位阻抑制有序的自组装和淀粉样蛋白的形成，