Department of Microbiology and Molecular Genetics, The Institute for Medical Research - Israel-Canada, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Bioinformatics. 2010 Oct 15;26(20):2564-70. doi: 10.1093/bioinformatics/btq495. Epub 2010 Aug 27.
Many protein-protein interactions (PPIs) are mediated by protein domains. The structural data of multi-domain PPIs reveal the domain pair (or pairs) that mediate a PPI, and implicitly also the domain pairs that are not involved in the interaction. By analyzing such data, preference relations between domain pairs as interaction mediators may be revealed.
Here, we analyze the differential use of domain pairs as mediators of stable interactions based on structurally solved multi-domain protein complexes. Our analysis revealed domain pairs that are preferentially used as interaction mediators and domain pairs that rarely or never mediate interaction, independent of the proteins' context. Between these extremes, there are domain pairs that mediate protein interaction in some protein contexts, while in other contexts different domain pairs predominate over them. By describing the preference relations between domain pairs as a network, we uncovered partial order and transitivity in these relations, which we further exploited for predicting interaction-mediating domains. The preferred domain pairs and the ones over which they predominate differ in several properties, but these differences cannot yet determine explicitly what underlies the differential use of domain pairs as interaction mediators. One property that stood up was the over-abundance of homotypic interactions among the preferred domain pairs, supporting previous suggestions on the advantages in the use of domain self-interaction for mediating protein interactions. Finally, we show a possible association between the preferred domain pairs and the function of the complex where they reside.
Supplementary data are available at Bioinformatics online.
许多蛋白质-蛋白质相互作用（PPIs）是由蛋白质结构域介导的。多结构域 PPIs 的结构数据揭示了介导 PPI 的结构域对（或多对），并且隐含地也揭示了不参与相互作用的结构域对。通过分析这些数据，可以揭示结构域对作为相互作用介体的偏好关系。
在这里，我们基于结构上已解决的多结构域蛋白质复合物，分析了稳定相互作用中结构域对作为介体的差异使用。我们的分析揭示了优先用作相互作用介体的结构域对和很少或从不介导相互作用的结构域对，而与蛋白质的上下文无关。在这些极端之间，有一些结构域对在某些蛋白质上下文中介导蛋白质相互作用，而在其他上下文中则优先使用其他结构域对。通过将结构域对之间的偏好关系描述为网络，我们揭示了这些关系中的偏序和传递性，我们进一步利用这些关系来预测相互作用介导的结构域。优先结构域对和它们占主导地位的结构域对在几个性质上有所不同，但这些差异还不能明确确定是什么导致了结构域对作为相互作用介体的差异使用。一个突出的性质是优先结构域对之间同源相互作用的过度丰富，支持了先前关于使用结构域自身相互作用来介导蛋白质相互作用的优势的建议。最后，我们展示了优先结构域对与它们所在复合物功能之间的可能关联。
补充数据可在“Bioinformatics”在线获取。
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