通过酸化调节FUS的液-液相分离:域特定补偿的作用
Si-Cheng Tong1, Jin Zhang1, Chen-Jiao Diao2
1State Key Laboratory of Supramolecular Structure and Materials, College of Chemistry, Jilin University, Changchun 130012, China.
The journal of physical chemistry. B
|January 14, 2026
概括
酸化调节FUS蛋白质凝聚物的形成. 这项研究揭示了全长FUS如何避免受损的液体-液体相分离 (LLPS) 和有毒聚合,与其低复杂性域 (LCD) 不同.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 生物物理学的生物物理.
背景情况:
- 通过液-液相分离 (LLPS) 形成的生物分子凝聚物对于细胞组织至关重要.
- RNA结合蛋白FUS通过LLPS形成动态凝聚物,其聚合与像ALS这样的神经退行性疾病有关.
- 在LLPS中酸化对FUS及其低复杂性域 (LCD) 的差异性影响在机理上仍然不清楚.
研究的目的:
- 研究酸化调节全长FUS凝聚物的形成和性质的分子机制.
- 为了比较酸化对全长FUS冷凝剂和FUS-LCD冷凝剂的影响.
- 为了阐明全长FUS如何保持凝结物的完整性,尽管有酸化.
主要方法:
- 用分子动力学模拟来分析野生型 (WT) 和化FUS凝聚物的结构特征.
- 在酸化条件下,比较全长FUS和FUS-LCD之间的凝结物行为.
- 开发一个模型来分析FUS冷凝液的粘性弹性.
主要成果:
- 全长FUS的酸化抑制了液滴转化为有毒聚合物,而不是阻止初始LLPS,通过其域之间的协同调节.
- 对于FUS-LCD,通过酸化减少LLPS与酸化位数直接相关.
- 由于酸化而改变了凝结体内的相互作用模式,这显著影响了它们的粘性弹性特性.
结论:
- 全长FUS采用补偿机制,以保持凝结物的完整性,并避免LLPS在酸化后的损害.
- 酸化对FUS冷凝物质性能的影响,包括粘性弹性,取决于领域和特定地点.
- 这项研究提供了分子洞察力,了解酸化如何微调FUS凝聚力学,可能为神经退行性疾病提供治疗点.
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