全长 hnRNPA1 粉样纤维的冷-EM 结构
Kartikay Sharma1, Sambhasan Banerjee1, Dilan Savran2
1Institute of Protein Biochemistry, Ulm University, 89081 Ulm, Germany.
Journal of molecular biology
|July 22, 2023
概括
异质核核核糖核蛋白A1 (hnRNPA1) 的粉样纤维具有复杂的结构. 一个短的核心部分形成了纤维,被一个无序的蛋白质外套所包围,挑战了当前的蛋白质错折理论.
科学领域:
- 生物化学 生物化学
- 结构生物学 结构生物学
- 神经科学是一个神经科学.
背景情况:
- 异质核核核糖核蛋白A1 (hnRNPA1) 与神经退行性疾病如ALS和多系统蛋白质病变有关.
- hnRNPA1是一种多功能RNA结合蛋白,涉及各种细胞过程.
研究的目的:
- 通过使用冷电子显微镜确定由全长 hnRNPA1 形成的粉样纤维的三维结构.
- 在神经退行性疾病的背景下了解 hnRNPA1 聚合的结构基础.
主要方法:
- 使用冷电子显微镜 (cryo-EM) 可视化纤维结构.
- 纤维细胞结构的分析,包括核心形成和周围的蛋白质元素.
主要成果:
- 纤维细胞核由来自类低复杂性域的45个残留部分组成.
- 其余的275个残留物在有序纤维细胞核周围形成了一个"模糊的外套".
- 纤维细胞表现出伪-21螺丝对称性,有两个堆叠的纤维细胞蛋白单元.
结论:
- hnRNPA1粉样纤维的结构比简单的蛋白质错折模型预测的要复杂得多.
- 与疾病相关的突变位于有序核心内,但不一定在最容易聚合的区域.
- 这些发现表明hnrnpa1聚合的新机制及其在神经退行中的作用.
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