Why are G-quadruplexes good at preventing protein aggregation?

Why are G-quadruplexes good at preventing protein aggregation?
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DOI:
10.1080/15476286.2023.2228572
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发表时间:
2023-01
期刊:
影响因子:
4.1
通讯作者:
Horowitz, Scott
Horowitz, Scott
中科院分区:
生物学3区
文献类型:
--
作者:
Litberg, Theodore J.;Sannapureddi, Rajesh Kumar Reddy;Huang, Zijue;Son, Ahyun;Sathyamoorthy, Bharathwaj;Horowitz, Scott

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维持健康的蛋白质折叠环境对细胞功能至关重要。最近,我们发现核酸,特别是G-四链体,是有效的分子伴侣,用于防止蛋白质聚集。借助两个G-四链体形成序列PARP-Ⅰ和LTR-Ⅲ的结构-功能和NMR分析,我们发现了几个影响G-四链体阻止蛋白质聚集的因素。值得注意的是,三个因素成为至关重要的决定保持酶活性的G-四链体:其结构拓扑结构,G-四链体的可及性和动力学,和寡聚状态。这些因素似乎在很大程度上决定了G-四链体是否能够防止部分错误折叠的蛋白质聚集。了解G-四链体调节蛋白质聚集能力的物理特性将有助于阐明它们在神经退行性疾病中可能的作用。
Maintaining a healthy protein folding environment is essential for cellular function. Recently, we found that nucleic acids, G-quadruplexes in particular, are potent chaperones for preventing protein aggregation. With the aid of structure-function and NMR analyses of two G-quadruplex forming sequences, PARP-I and LTR-III, we uncovered several contributing factors that affect G-quadruplexes in preventing protein aggregation. Notably, three factors emerged as vital in determining holdase activity of G-quadruplexes: their structural topology, G-quadruplex accessibility and dynamics, and oligomerization state. These factors together appear to largely dictate whether a G-quadruplex is able to prevent partially misfolded proteins from aggregating. Understanding the physical traits that govern the ability of G-quadruplexes to modulate protein aggregation will help elucidate their possible roles in neurodegenerative disease.
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