G-Quadruplexes act as sequence-dependent protein chaperones.
G-Quadruplexes act as sequence-dependent protein chaperones.
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DOI：
10.15252/embr.201949735
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发表时间：
2020-10-05
期刊：
影响因子：
7.7
通讯作者：
Horowitz S
中科院分区：
文献类型：
--
作者：
Begeman A;Son A;Litberg TJ;Wroblewski TH;Gehring T;Huizar Cabral V;Bourne J;Xuan Z;Horowitz S
维持蛋白质组的健康对细胞的存活很重要。核酸具有比传统伴侣蛋白更有效地防止蛋白质聚集的能力。在这项研究中，我们探讨了核酸分子伴侣活性的序列特异性。评估超过500个核酸序列对蛋白质聚集的影响，我们表明核酸的保持酶伴侣效应是序列依赖性的。G-四链体通过四链体防止蛋白质聚集：蛋白质寡聚化。它们还增加了大肠杆菌中生物传感器的折叠蛋白水平。这些观察结果使最近关于四链体在聚集相关疾病（如脆性X和肌萎缩侧索硬化症（ALS））中发挥重要作用的报道背景化，并提供了核酸能够调节大肠杆菌折叠环境的证据。检查核酸分子伴侣活性的序列依赖性发现四链体在蛋白质寡聚化和聚集预防中具有有效作用。
Maintaining proteome health is important for cell survival. Nucleic acids possess the ability to prevent protein aggregation more efficiently than traditional chaperone proteins. In this study, we explore the sequence specificity of the chaperone activity of nucleic acids. Evaluating over 500 nucleic acid sequences’ effects on protein aggregation, we show that the holdase chaperone effect of nucleic acids is sequence‐dependent. G‐Quadruplexes prevent protein aggregation via quadruplex:protein oligomerization. They also increase the folded protein level of a biosensor in E. coli. These observations contextualize recent reports of quadruplexes playing important roles in aggregation‐related diseases, such as fragile X and amyotrophic lateral sclerosis (ALS), and provide evidence that nucleic acids have the ability to modulate the folding environment of E. coli. Examining nucleic acids for the sequence dependence of their chaperone activity finds quadruplexes have potent roles in protein oligomerization and aggregation prevention.