DAXX代表了一种新型的蛋白质折叠促进剂
Liangqian Huang1,2, Trisha Agrawal1,2,3, Guixin Zhu1,2
1Department of Cancer Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Nature
|August 19, 2021
概括
富含多Asp/ Glu (多D/ E) 的DAXX蛋白质作为一个独立于ATP的分子伴侣. 它可以防止和逆转蛋白质聚合,为细胞蛋白质质量控制提供一种新的机制.
科学领域:
- 细胞生物学
- 生物化学
- 分子生物学
背景情况:
- 蛋白质质量控制对于细胞功能和生物体健康至关重要.
- 现有系统通常涉及依赖ATP的多元件机器.
- 具有广泛电荷的多Asp/Glu (多D/E) 蛋白质的功能在很大程度上仍未被定义.
研究的目的:
- 研究DAXX的生物化学活动,一个多Asp/Glu (polyD/E) 蛋白质.
- 确定多D/E蛋白是否可以作为新型蛋白质质量控制系统.
- 探索DAXX在管理蛋白质聚合和折叠方面的潜力.
主要方法:
- 使用模型基质和神经退行相关蛋白质评估DAXX预防和逆转蛋白质聚合的能力.
- 研究了DAXX对容易聚合的客户端蛋白质p53和MDM2的影响.
- 检查了多Asp/Glu (多D/E) 区域在DAXX的陪伴活性中的作用.
- 对其他多Asp/Glu (多D/E) 蛋白质 (ANP32A,SET) 进行了类似活动的测试.
主要成果:
- DAXX表现出显著的蛋白质折叠活动,包括防止聚合,溶解聚合物和展开错误折叠的蛋白质.
- DAXX有效地阻止并逆转其客户端蛋白质p53和MDM2的聚合.
- DAXX恢复了聚合易感的p53突变体的原生形状和功能,减少了致癌性质.
- 这些活动与ATP无关,依赖于多Asp/Glu (polyD/E) 区域.
- 其他多Asp/Glu (多D/E) 蛋白质也可以作为ATP独立的辅助蛋白,分聚酶和解酶.
结论:
- DAXX所示的多-Asp/Glu (多D/E) 蛋白质代表了一类独立于ATP的分子伴侣蛋白.
- 这些蛋白质构成一种能够控制蛋白质聚合和错误折叠的新型多功能蛋白质质量控制系统.
- DAXX能够重新折叠突变的p53为癌症治疗提供了潜在的治疗途径.
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