一个RNA结合蛋白低复杂性域的老化液滴的刚性核心的识别
Blake D Fonda1, Khaled M Jami1, Natalie R Boulos1
1Department of Chemistry, University of California, Davis, California 95616, United States.
Journal of the American Chemical Society
|April 26, 2021
概括
生物分子凝结形成液滴, 对于细胞功能和疾病至关重要. 这项研究表明,TDP-43蛋白纤维素可以在先前识别的病理区域之外形成结构化的核心,这表明纤维素形成的复杂动态.
科学领域:
- 生物化学和分子生物学
- 神经科学
- 生物物理
背景情况:
- 低复杂度序列的蛋白质的生物分子凝聚对于RNA代谢至关重要,并与神经退行性疾病有关.
- 液滴通过缩生物分子来促进细胞功能,但它们的硬化成病态水凝尚不清楚.
- 低复杂度的序列可以包含多个易发生纤维的区域,平衡功能和病理相互作用.
研究的目的:
- 通过TARDNA结合蛋白43 (TDP-43) 的低复杂性域形成的液滴的成熟过程.
- 确定TDP-43液滴中的结构核心及其与已知的病理区域的关系.
主要方法:
- 使用TDP-43的低复杂性域形成和老化液滴.
- 固态核磁共振 (ssNMR) 光谱分析老化滴的结构.
主要成果:
- ssNMR发现残留物365-400是老化的TDP-43液滴的结构核心.
- 这种结构化的核心位于先前涉及的病理纤维形成区域 (残留物311-360) 外.
- 结果表明TDP-43低复杂性域内的多个细分容易形成纤维.
结论:
- 这项研究挑战了TDP-43中纤维形成仅限于特定区域的概念.
- 在一个段中稳定β链丰富的结构可以抑制蛋白质的其他区域的纤维形成.
- 这为液滴动力学,纤维细胞形成和神经退行性疾病发病之间的复杂相互作用提供了新的见解.
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