Lysine and Arginine Content of Proteins: Computational Analysis Suggests a New Tool for Solubility Design
Lysine and Arginine Content of Proteins: Computational Analysis Suggests a New Tool for Solubility Design
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DOI：
10.1021/mp4004749
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发表时间：
2014-01-01
影响因子：
4.9
通讯作者：
Curtis, Robin A.
中科院分区：
文献类型：
--
作者：
Warwicker, Jim;Charonis, Spyros;Curtis, Robin A.
蛋白质溶解度的预测和工程是一个重要但不精确的领域。虽然常规使用了一些特征，例如避免了广泛的非极性表面积，但仍有余地利用实验数据对序列和结构特征进行基准测试。我们在实验溶解度、蛋白基因表达水平和丰富蛋白（血清白蛋白和肌红蛋白）家族及其不太丰富的类似物的背景下研究特性。具有较高溶解度、较高表达和丰度水平的蛋白质的一个共同特征是赖氨酸含量与精氨酸含量的比例增加。我们认为，精氨酸的相同性质导致了它对特定相互作用表面的记录倾向，也导致了在非特异性接触处的有利相互作用，因此赖氨酸在相对高浓度时更适合蛋白质。一项对蛋白质疗法的调查显示，一个重要的亚群具有相对较低的赖氨酸与精氨酸比例，因此可能不适合高蛋白浓度。我们得出的结论是，赖氨酸和精氨酸含量的调节可以证明是一个有用的和相对简单的添加到生物技术应用中工程蛋白溶解度可用的工具包中。
Prediction and engineering of protein solubility is an important but imprecise area. While some features are routinely used, such as the avoidance of extensive non-polar surface area, scope remains for benchmarking of sequence and structural features with experimental data. We study properties in the context of experimental solubilities, protein gene expression levels, and families of abundant proteins (serum albumin and myoglobin) and their less abundant paralogues. A common feature that emerges for proteins with elevated solubility and at higher expression and abundance levels is an increased ratio of lysine content to arginine content. We suggest that the same properties of arginine that give rise to its recorded propensity for specific interaction surfaces also lead to favorable interactions at nonspecific contacts, and thus lysine is favored for proteins at relatively high concentration. A survey of protein therapeutics shows that a significant subset possesses a relatively low lysine to arginine ratio, and therefore may not be favored for high protein concentration. We conclude that modulation of lysine and arginine content could prove a useful and relatively simple addition to the toolkit available for engineering protein solubility in biotechnological applications.