Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins
Bimodal protein solubility distribution revealed by an aggregation analysis of the entire ensemble of Escherichia coli proteins
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DOI：
10.1073/pnas.0811922106
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发表时间：
2009-03-17
影响因子：
11.1
通讯作者：
Taguchi, Hideki
中科院分区：
文献类型：
--
作者：
Niwa, Tatsuya;Ying, Bei-Wen;Taguchi, Hideki
蛋白质折叠通常与分子间聚集竞争，这在大多数情况下不可逆地损害蛋白质功能，如包涵体的形成所例示。尽管已经凭经验确定一些蛋白质倾向于聚集，但蛋白质聚集倾向与一级序列之间的关系仍然知之甚少。在这里，我们单独合成的大肠杆菌蛋白质的整个合奏，通过使用体外重建的翻译系统和分析的聚集倾向。由于重组的翻译系统是无分子伴侣的，我们可以评估成千上万的蛋白质的固有聚集倾向，在一个预防耦合的方式。基于来自3，173个翻译蛋白质的数据的溶解度直方图显示出明显的双峰分布，表明聚集倾向在连续体中不是均匀分布的。相反，蛋白质可以分为2组，可溶性和易于聚集的蛋白质。聚集倾向与蛋白质的结构分类最显著相关，这意味着聚集倾向的预测需要关于蛋白质的结构信息。
Protein folding often competes with intermolecular aggregation, which in most cases irreversibly impairs protein function, as exemplified by the formation of inclusion bodies. Although it has been empirically determined that some proteins tend to aggregate, the relationship between the protein aggregation propensities and the primary sequences remains poorly understood. Here, we individually synthesized the entire ensemble of Escherichia coli proteins by using an in vitro reconstituted translation system and analyzed the aggregation propensities. Because the reconstituted translation system is chaperone-free, we could evaluate the inherent aggregation propensities of thousands of proteins in a translation-coupled manner. A histogram of the solubilities, based on data from 3,173 translated proteins, revealed a clear bimodal distribution, indicating that the aggregation propensities are not evenly distributed across a continuum. Instead, the proteins can be categorized into 2 groups, soluble and aggregation-prone proteins. The aggregation propensity is most prominently correlated with the structural classification of proteins, implying that the prediction of aggregation propensity requires structural information about the protein.