Structural similarity enhances interaction propensity of proteins
Structural similarity enhances interaction propensity of proteins
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DOI：
10.1016/j.jmb.2006.11.020
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发表时间：
2007-02-02
影响因子：
5.6
通讯作者：
Shakhnovich, E. I.
中科院分区：
文献类型：
--
作者：
Lukatsky, D. B.;Shakhnovich, B. E.;Shakhnovich, E. I.
我们研究了相互作用的蛋白质样表面的统计特性，并预测了两种强大的相关效应：(i)统计增强的蛋白质自吸引；（ii）具有相似结构的蛋白质在统计学上的吸引力增强。这种效应源于这样一个事实，即在两个相同的、甚至是随机组织的相互作用的蛋白质表面之间找到模式自匹配的概率总是高于在两个不同的、混杂的蛋白质表面之间找到模式自匹配的概率。这一理论发现解释了先前报道的蛋白质-蛋白质相互作用网络中同型二聚体的统计普遍性。此外，我们的研究结果通过对蛋白质复合物数据库的分析得到了证实，该数据库显示出高度统计学上显著的过度代表性。由结构相似但序列高度分化的蛋白质形成的二聚体（“超家族异二聚体”）。我们认为混杂的同型二聚体相互作用对由同型二聚体进化而来的异源二聚体构成了强烈的竞争性相互作用。这样的进化瓶颈是克服使用负设计进化压力适用于滥交同型二聚体的形成。这是通过在模型和真实的超家族异源二聚体中由带电残基形成的高度特异性接触来实现的。(c) 2006 Elsevier Ltd.版权所有。
We study statistical properties of interacting protein-like surfaces and predict two strong, related effects: (i) statistically enhanced self-attraction of proteins; (ii) statistically enhanced attraction of proteins with similar structures. The effects originate in the fact that the probability to find a pattern self-match between two identical, even randomly organized interacting protein surfaces is always higher compared with the probability for a pattern match between two different, promiscuous protein surfaces. This theoretical finding explains statistical prevalence of homodimers in protein-protein interaction networks reported earlier. Further, our findings are confirmed by the analysis of curated database of protein complexes that showed highly statistically significant overrepresentation. of dimers formed by structurally similar proteins with highly divergent sequences ("superfamily heterodimers"). We suggest that promiscuous homodimeric interactions pose strong competitive interactions for heterodimers evolved from homodimers. Such evolutionary bottleneck is overcome using the negative design evolutionary pressure applied against promiscuous homodimer formation. This is achieved through the formation of highly specific contacts formed by charged residues as demonstrated both in model and real superfamily heterodimers. (c) 2006 Elsevier Ltd. All rights reserved.