Salt-Dependent Conformational Changes of Intrinsically Disordered Proteins
Salt-Dependent Conformational Changes of Intrinsically Disordered Proteins
复制标题
本质无序蛋白质的盐依赖性构象变化
DOI：
10.1021/acs.jpclett.1c01607
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Zheng, Wenwei
中科院分区：
文献类型：
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作者：
Wohl, Samuel;Jakubowski, Matthew;Zheng, Wenwei
已知固有无序蛋白（IDP）的柔性结构会受到盐浓度的干扰，这可以通过带电氨基酸的静电屏蔽来理解。然而，IDP通常含有更多受盐析效应影响的不带电残基。在这里，我们已经参数化的盐析效果到一个粗粒度的模型，使用一组Fo的共振能量转移数据和验证与实验盐依赖性的液-液相分离（LLPS）的17种蛋白质。新模型可以正确捕获6个序列的行为，当盐浓度变化时，总共有13个序列。连同超过500 IDP序列的调查，我们得出结论，盐析效应，这被认为是次要的静电筛选，是重要的IDP序列与适度带电的残基在生理盐浓度。所提出的方案是普遍适用于其他计算模型捕获盐依赖IDP构象。
The flexible structure of an intrinsically disordered protein (IDP) is known to be perturbed by salt concentrations, which can be understood by electrostatic screening on charged amino acids. However, an IDP usually contains more uncharged residues that are influenced by the salting-out effect. Here we have parametrized the salting-out effect into a coarse-grained model using a set of Förster resonance energy transfer data and verified with experimental salt-dependent liquid–liquid phase separation (LLPS) of 17 proteins. The new model can correctly capture the behavior of 6 more sequences, resulting in a total of 13 when varying salt concentrations. Together with a survey of more than 500 IDP sequences, we conclude that the salting-out effect, which was considered to be secondary to electrostatic screening, is important for IDP sequences with moderately charged residues at physiological salt concentrations. The presented scheme is generally applicable to other computational models for capturing salt-dependent IDP conformations.