Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome
Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome
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DOI：
10.1073/pnas.1812756115
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发表时间：
2018-10-02
影响因子：
11.1
通讯作者：
von Heijne, Gunnar
中科院分区：
文献类型：
--
作者：
Farias-Rico, Jose Arcadio;Selin, Frida Ruud;von Heijne, Gunnar
在过去的五十年里，对蛋白质在稀缓冲液中折叠的研究为这一复杂的过程提供了丰富的图景。然而，在细胞中，蛋白质可以在仍然附着在核糖体上的情况下开始折叠(共翻译折叠)，目前还不清楚核糖体如何影响不同大小、热力学稳定性和净电荷的蛋白质结构域的折叠。在这里，通过使用阻止肽作为力传感器和核糖体上的脉冲蛋白分解，我们提供了一个全面的图像，说明了蛋白质折叠的核糖体中肽转移酶中心的距离如何与蛋白质大小相关。此外，对大肠杆菌核糖体蛋白56的大量突变体的分析表明，蛋白质折叠对新生链条的作用力与折叠状态的热力学稳定性呈线性关系，核糖体环境不利于高净负电荷结构域的折叠。
During the last five decades, studies of protein folding in dilute buffer solutions have produced a rich picture of this complex process. In the cell, however, proteins can start to fold while still attached to the ribosome (cotranslational folding) and it is not yet clear how the ribosome affects the folding of protein domains of different sizes, thermodynamic stabilities, and net charges. Here, by using arrest peptides as force sensors and on-ribosome pulse proteolysis, we provide a comprehensive picture of how the distance from the peptidyl transferase center in the ribosome at which proteins fold correlates with protein size. Moreover, an analysis of a large collection of mutants of the Escherichia coli ribosomal protein 56 shows that the force exerted on the nascent chain by protein folding varies linearly with the thermodynamic stability of the folded state, and that the ribosome environment disfavors folding of domains of high net-negative charge.