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由C9orf72重复扩张向LC域聚合物编码的有毒PR多
Yi Lin1, Eiichiro Mori1, Masato Kato1
1Department of Biochemistry, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9152, USA.
Cell
|October 22, 2016
概括
研究人员确定了有毒的PR多
科学领域:
- 神经科学
- 分子生物学
- 细胞生物学
背景情况:
- 肌缩侧面硬化 (ALS) 是一种神经退行性疾病.
- C9orf72基因突变是家族性ALS的一个常见原因.
- 有毒的二重复蛋白 (DPR) 参与了C9orf72-ALS的发病.
研究的目的:
- 为了确定有毒的PR多的细胞内标.
- 了解ALS中PR中介细胞毒性的机制.
主要方法:
- 使用两种互补的生化方法来分离PR结合蛋白.
- 分析了蛋白质-蛋白质相互作用和域特异性.
主要成果:
- 在低复杂性 (LC) 序列中与富含蛋白质结合的PR多.
- 这些LC序列是PR多的直接结合标.
- PR与LC域的结合取决于聚合物.
结论:
- 在C9orf72-ALS中,PR介导的毒性可能源于细胞结构和基因表达的破坏.
- 这种蛋白质会干扰细胞动态和信息流.
- 了解公关目标可以了解ALS的机制.
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