Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
J Mol Biol. 2011 Jun 10;409(3):439-49. doi: 10.1016/j.jmb.2011.03.056. Epub 2011 Apr 2.
Numerous experiments demonstrate a high level of promiscuity and structural disorder in organismal proteomes. Here, we ask the question what makes a protein promiscuous, that is, prone to nonspecific interactions, and structurally disordered. We predict that multi-scale correlations of amino acid positions within protein sequences statistically enhance the propensity for promiscuous intra- and inter-protein binding. We show that sequence correlations between amino acids of the same type are statistically enhanced in structurally disordered proteins and in hubs of organismal proteomes. We also show that structurally disordered proteins possess a significantly higher degree of sequence order than structurally ordered proteins. We develop an analytical theory for this effect and predict the robustness of our conclusions with respect to the amino acid composition and the form of the microscopic potential between the interacting sequences. Our findings have implications for understanding molecular mechanisms of protein aggregation diseases induced by the extension of sequence repeats.
大量实验表明,生物体系的蛋白质组具有高度的混杂性和结构无序性。在这里,我们提出一个问题:是什么使蛋白质具有混杂性,即易于发生非特异性相互作用和结构无序。我们预测,蛋白质序列中氨基酸位置的多尺度相关性会在统计上增强蛋白质内部和蛋白质之间混杂性结合的倾向性。我们表明,在结构无序的蛋白质中和在生物体系蛋白质组的枢纽中,同种类型氨基酸之间的序列相关性在统计上是增强的。我们还表明,结构无序的蛋白质具有比结构有序的蛋白质更高的序列有序度。我们为此效应建立了一个分析理论,并预测了我们的结论在氨基酸组成和相互作用序列之间微观势的形式方面的稳健性。我们的发现对于理解由序列重复扩展引起的蛋白质聚集疾病的分子机制具有重要意义。