Binding interface change and cryptic variation in the evolution of protein-protein interactions.
Binding interface change and cryptic variation in the evolution of protein-protein interactions.
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DOI：
10.1186/s12862-016-0608-1
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发表时间：
2016-02-18
影响因子：
3.4
通讯作者：
Lovell SC
中科院分区：
文献类型：
--
作者：
Ames RM;Talavera D;Williams SG;Robertson DL;Lovell SC
蛋白质之间的物理相互作用对于几乎所有的生物功能和系统都是必不可少的。为了理解功能的进化，理解分子相互作用的进化是很重要的。关键的重要性是结合特异性的进化，由蛋白质产生的相互作用的集合，因为特异性的变化可以导致相互作用网络的“重新布线”。不幸的是，蛋白质相互作用的界面是复杂的，通常含有许多氨基酸残基，这些氨基酸残基共同必须有助于结合特异性以及结合亲和力、界面的结构完整性和未结合状态下的溶解度。为了研究界面组成和结合特异性之间的关系，我们利用旁系同源对酵母蛋白。复制后，这些旁系同源物将立即具有相同的序列和蛋白质产物，从而产生相同的相互作用。随着序列的不同，我们可以将界面上的氨基酸变化与结合特异性的任何变化联系起来。我们发现，界面区域的变化仅与特异性的变化弱相关，并且界面中的许多变体在功能上是等同的。我们发现，许多接口内的残基置换是沉默的，他们的贡献结合特异性。我们的结论是，这样的功能等效的变化有可能有助于进化可塑性的接口，通过创建神秘的变化，这反过来又可能提供原材料的功能创新和共同进化。本文的在线版本（doi：10.1186/s12862-016-0608-1）包含补充材料，可供授权用户使用。
Physical interactions between proteins are essential for almost all biological functions and systems. To understand the evolution of function it is therefore important to understand the evolution of molecular interactions. Of key importance is the evolution of binding specificity, the set of interactions made by a protein, since change in specificity can lead to “rewiring” of interaction networks. Unfortunately, the interfaces through which proteins interact are complex, typically containing many amino-acid residues that collectively must contribute to binding specificity as well as binding affinity, structural integrity of the interface and solubility in the unbound state. In order to study the relationship between interface composition and binding specificity, we make use of paralogous pairs of yeast proteins. Immediately after duplication these paralogues will have identical sequences and protein products that make an identical set of interactions. As the sequences diverge, we can correlate amino-acid change in the interface with any change in the specificity of binding. We show that change in interface regions correlates only weakly with change in specificity, and many variants in interfaces are functionally equivalent. We show that many of the residue replacements within interfaces are silent with respect to their contribution to binding specificity. We conclude that such functionally-equivalent change has the potential to contribute to evolutionary plasticity in interfaces by creating cryptic variation, which in turn may provide the raw material for functional innovation and coevolution. The online version of this article (doi:10.1186/s12862-016-0608-1) contains supplementary material, which is available to authorized users.