Bioinformatics and Functional Genomics Research Group, Cancer Research Center (CIC-IBMCC, CSIC/USAL), Consejo Superior de Investigaciones Científicas, Salamanca, Spain.
Proteins. 2010 Jan;78(1):109-17. doi: 10.1002/prot.22569.
Assessment and improvement of the reliability of protein-protein interaction (ppi) data is critical for the progress of the currently active research on interactomes. Some interesting questions in this respect are: How three-dimensional (3D) protein structural data is present in known ppi data?, and How this kind of information can be used to validate and improve the interactomes? To address this problem, analysis and unification of six structural domain-domain interaction (sddi) datasets is presented; followed by a comparative study of these sddi data in three ppi reference sets produced at different levels of confidence. The results show that protein structural and interactomic data are partially complementary and that a larger proportion of structural information is observed in more confident interactomes. We also present, focused on the human interactome, an analysis of the domains that are more frequently present in: (i) an interactome based on validation by at least two experimental methods versus (ii) another interactome based on validation by 3D structural interaction data. These results allow to distinguish between domain pairs associated to protein interactions supported by 3D structures and domain pairs that at present are not supported by structural information. The domain pairs exclusive of interactions without associated 3D data reveal interacting conserved modules that are probably flexible, disordered, and difficult to crystallize; and which are often found in proteins involved in signaling pathways and DNA processing.
评估和提高蛋白质-蛋白质相互作用 (PPI) 数据的可靠性对于目前活跃的互作组研究进展至关重要。在这方面有一些有趣的问题：三维 (3D) 蛋白质结构数据在已知的 PPI 数据中是如何呈现的？这种信息如何用于验证和改进互作组？为了解决这个问题，本文对六个结构域-域相互作用 (SDDI) 数据集进行了分析和统一；随后对三种不同置信度水平生成的三个 PPI 参考集中的这些 SDDI 数据进行了比较研究。结果表明，蛋白质结构和互作组数据部分互补，结构信息在更可信的互作组中观察到的比例更大。我们还集中于人类互作组，分析了在以下两种情况中更频繁出现的结构域：(i) 通过至少两种实验方法验证的互作组与 (ii) 通过 3D 结构相互作用数据验证的另一个互作组。这些结果可以区分与由 3D 结构支持的蛋白质相互作用相关的结构域对和目前不支持结构信息的结构域对。与没有相关 3D 数据的相互作用排他的结构域对揭示了可能是灵活的、无序的、难以结晶的相互作用保守模块；它们经常存在于参与信号通路和 DNA 处理的蛋白质中。
