G-quadruplexes rescuing protein folding.
G-quadruplexes rescuing protein folding.
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DOI：
10.1073/pnas.2216308120
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发表时间：
2023-05-16
影响因子：
11.1
通讯作者：
Horowitz, Scott
中科院分区：
文献类型：
--
作者：
Son, Ahyun;Cabral, Veronica Huizar;Huang, Zijue;Litberg, Theodore J.;Horowitz, Scott
正确管理蛋白质折叠和聚集对于细胞健康至关重要，许多疾病都是由这些过程中的错误引起的。虽然核酸长期以来一直被认为在蛋白质折叠和聚集中发挥作用，但核酸是否可以直接影响蛋白质折叠仍不清楚。在这里，我们表明，与典型的不依赖于 ATP 的“保持酶”机制不同，G-四链体可以触发蛋白质折叠。这些结果拓宽了细胞可用于指导蛋白质折叠的策略集。维持蛋白质组的健康是一项重要的细胞任务。最近，我们发现 G-四链体 (G4) 核酸在体外特别有效地防止蛋白质聚集，并且至少可以间接改善大肠杆菌的蛋白质折叠环境。然而，G4 在蛋白质折叠中的作用尚未被探索。在这里，通过体外蛋白质折叠实验，我们发现 G4 可以通过将动力学捕获的中间体拯救为天然和近天然折叠状态来加速蛋白质折叠。大肠杆菌中的时程折叠实验进一步证明，这些 G4 主要改善大肠杆菌中的蛋白质折叠质量，而不是防止蛋白质聚集。短核酸拯救蛋白质折叠的能力开启了核酸和不依赖ATP的分子伴侣在决定蛋白质最终折叠命运方面发挥重要作用的可能性。
Correctly managing protein folding and aggregation is critical to cellular health, with many diseases resulting from mistakes in these processes. While nucleic acids have long been implicated as playing a role in protein folding and aggregation, whether nucleic acids could directly impact protein folding remained unclear. Here, we show that unlike a typical ATP-independent “holdase” mechanism, G-quadruplexes can trigger protein folding. These results broaden the set of strategies that can be used by the cell to guide protein folding. Maintaining the health of the proteome is a critical cellular task. Recently, we found G-quadruplex (G4) nucleic acids are especially potent at preventing protein aggregation in vitro and could at least indirectly improve the protein folding environment of Escherichia coli. However, the roles of G4s in protein folding were not yet explored. Here, through in vitro protein folding experiments, we discover that G4s can accelerate protein folding by rescuing kinetically trapped intermediates to both native and near-native folded states. Time-course folding experiments in E. coli further demonstrate that these G4s primarily improve protein folding quality in E. coli as opposed to preventing protein aggregation. The ability of a short nucleic acid to rescue protein folding opens up the possibility of nucleic acids and ATP-independent chaperones to play considerable roles in dictating the ultimate folding fate of proteins.
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折叠，绑定到伴侣。
影响因子：
6.8
作者：
Horowitz S;Koldewey P;Stull F;Bardwell JC
通讯作者：
Bardwell JC
影响因子：
7.7
作者：
Begeman A;Son A;Litberg TJ;Wroblewski TH;Gehring T;Huizar Cabral V;Bourne J;Xuan Z;Horowitz S
通讯作者：
Horowitz S
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影响因子：
14.9
作者：
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通讯作者：
Pastré D
影响因子：
3.6
作者：
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通讯作者：
Hengge, Regine
影响因子：
5.6
作者：
Haslbeck, Martin;Vierling, Elizabeth
通讯作者：
Vierling, Elizabeth