Laboratory of Nuclear Magnetic Resonance, Fundación Instituto Leloir, IIBBA-CONICET, Av. Patricias Argentinas 435, C1405BWE, CABA, Argentina.
Sci Rep. 2018 Jul 13;8(1):10618. doi: 10.1038/s41598-018-29035-z.
Production of soluble recombinant proteins is crucial to the development of industry and basic research. However, the aggregation due to the incorrect folding of the nascent polypeptides is still a mayor bottleneck. Understanding the factors governing protein solubility is important to grasp the underlying mechanisms and improve the design of recombinant proteins. Here we show a quantitative study of the expression and solubility of a set of proteins from Bizionia argentinensis. Through the analysis of different features known to modulate protein production, we defined two parameters based on the %MinMax algorithm to compare codon usage clusters between the host and the target genes. We demonstrate that the absolute difference between all %MinMax frequencies of the host and the target gene is significantly negatively correlated with protein expression levels. But most importantly, a strong positive correlation between solubility and the degree of conservation of codons usage clusters is observed for two independent datasets. Moreover, we evince that this correlation is higher in codon usage clusters involved in less compact protein secondary structure regions. Our results provide important tools for protein design and support the notion that codon usage may dictate translation rate and modulate co-translational folding.
可溶性重组蛋白的生产对工业和基础研究的发展至关重要。然而，由于新生多肽的错误折叠导致的聚集仍然是一个主要的瓶颈。了解影响蛋白质可溶性的因素对于掌握潜在机制和改进重组蛋白的设计很重要。在这里，我们展示了对 Bizionia argentinensis 中一组蛋白质的表达和可溶性的定量研究。通过分析已知调节蛋白质生产的不同特征，我们根据 %MinMax 算法定义了两个参数，用于比较宿主和目标基因之间的密码子使用簇。我们证明，宿主和目标基因的所有 %MinMax 频率的绝对差异与蛋白质表达水平呈显著负相关。但最重要的是，对于两个独立的数据集，观察到了溶解度与密码子使用簇保守性程度之间的强正相关。此外，我们证明，这种相关性在涉及蛋白质二级结构区域不紧凑的密码子使用簇中更高。我们的结果为蛋白质设计提供了重要工具，并支持密码子使用可能决定翻译速率并调节共翻译折叠的观点。
