Functional site plasticity in domain superfamilies.
Functional site plasticity in domain superfamilies.
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DOI：
10.1016/j.bbapap.2013.02.042
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Orengo CA
中科院分区：
文献类型：
--
作者：
Dessailly BH;Dawson NL;Mizuguchi K;Orengo CA
据我们所知，我们首次对同源结构域超家族中的功能位点多样性进行了定量分析。不同类型的功能位点被分别考虑。我们的结果表明，就功能位点的空间位置而言，大多数多样的超家族具有很强的可塑性。对于蛋白质 - 蛋白质相互作用界面来说尤其如此。相反，我们证实催化位点通常只占据极少数的拓扑位置。小分子配体结合位点比预期的更加多样，尽管其多样性程度比蛋白质 - 蛋白质相互作用界面更有限。尽管观察到了多样性，但我们的结果也证实了先前报道的功能位点的优先位置。我们确定了一个同源结构域超家族的子集，其中多样性特别极端，并讨论了这种可塑性（即结构多样性）的可能原因。我们的结果与先前关于同源物之间位点优先共定位的报道并不矛盾，而是指出了不忽视其他位点的重要性，特别是在大型且多样的超家族中。在每个注释良好的结构域超家族内，不同亲缘关系所利用的位点数据已可从CATH网站获取，以突出通用的超家族或具有高度优先位点的超家族。这些信息对系统生物学很有价值，并且对蛋白质相互作用的任何限制的了解都有助于理解这些蛋白质所参与的网络的动态控制。我们工作的新颖之处在于分析的全面性——我们使用了比先前研究大得多的数据集——并且在许多超家族中我们表明，不同的亲缘关系利用结构域表面的不同部分进行配体/蛋白质相互作用，特别是在序列和结构多样的超家族中，这种大规模的观察结果先前未曾报道过。本文是题为“蛋白质的新兴动态观点：变构、进化和自组装中的蛋白质可塑性”特刊的一部分。
大多数多样的结构域超家族具有非常多样的功能位点位置。
催化位点位于少数受限的拓扑位置。
小分子配体结合位点的位置比预期的更加多样。
蛋白质 - 蛋白质相互作用界面在功能位点位置上表现出最大的灵活性。
We present, to our knowledge, the first quantitative analysis of functional site diversity in homologous domain superfamilies. Different types of functional sites are considered separately. Our results show that most diverse superfamilies are very plastic in terms of the spatial location of their functional sites. This is especially true for protein–protein interfaces. In contrast, we confirm that catalytic sites typically occupy only a very small number of topological locations. Small-ligand binding sites are more diverse than expected, although in a more limited manner than protein–protein interfaces. In spite of the observed diversity, our results also confirm the previously reported preferential location of functional sites. We identify a subset of homologous domain superfamilies where diversity is particularly extreme, and discuss possible reasons for such plasticity, i.e. structural diversity. Our results do not contradict previous reports of preferential co-location of sites among homologues, but rather point at the importance of not ignoring other sites, especially in large and diverse superfamilies. Data on sites exploited by different relatives, within each well annotated domain superfamily, has been made accessible from the CATH website in order to highlight versatile superfamilies or superfamilies with highly preferential sites. This information is valuable for system biology and knowledge of any constraints on protein interactions could help in understanding the dynamic control of networks in which these proteins participate. The novelty of our work lies in the comprehensive nature of the analysis – we have used a significantly larger dataset than previous studies – and the fact that in many superfamilies we show that different parts of the domain surface are exploited by different relatives for ligand/protein interactions, particularly in superfamilies which are diverse in sequence and structure, an observation not previously reported on such a large scale. This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, evolution and self-assembly. Most diverse domain superfamilies have very diverse functional site locations. Catalytic sites are found in a small, restricted number of topological positions. Location of small-ligand binding sites is more diverse than expected. Protein–protein interfaces display the most flexibility in functional site locations.
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