Paludo Gabriela Prado, Lorenzatto Karina Rodrigues, Bonatto Diego, Ferreira Henrique Bunselmeyer
Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, UFRGS, Porto Alegre, RS, Brazil.
Comput Biol Chem. 2015 Oct;58:1-8. doi: 10.1016/j.compbiolchem.2015.04.010. Epub 2015 Apr 21.
Glycolytic enzymes, such as enolase, have been described as multifunctional complex proteins that also display non-glycolytic activities, termed moonlighting functions. Although enolase multifunctionality has been described for several organisms, the conservation of enolase alternative functions through different phyla has not been explored with more details. A useful strategy to investigate moonlighting functions is the use of systems biology tools, which allow the prediction of protein functions/interactions by graph design and analysis. In this work, available information from protein-protein interaction (PPI) databases were used to design enolase PPI networks for four eukaryotic organisms, namely Homo sapiens, Drosophila melanogaster, Caenorhabditis elegans, and Saccharomyces cerevisiae, covering a wide spectrum of this domain of life. PPI networks with number of nodes ranging from 140 to 411 and up to 15,855 connections were generated, and modularity and centrality analyses, and functional enrichment were performed for all of them. The performed analyses showed that enolase is a central node within the networks, and that, in addition to its canonical interactions with proteins related to glycolysis and energetic metabolism, it is also part of protein clusters related to different biological processes, like transcription, development, and apoptosis, among others. Some of these non-glycolytic clusters, are partially conserved between networks, in terms of overall sharing of orthologs, overall cluster structure, and/or at the levels of key regulatory proteins within clusters. Overall, our results provided evidences of enolase multifunctionality and evolutionary conservation of enolase PPIs at all these levels.
糖酵解酶，如烯醇化酶，已被描述为多功能复合蛋白，它们还具有非糖酵解活性，称为兼职功能。尽管已经描述了几种生物体中烯醇化酶的多功能性，但尚未更详细地探索不同门类中烯醇化酶替代功能的保守性。研究兼职功能的一种有用策略是使用系统生物学工具，该工具允许通过图形设计和分析来预测蛋白质功能/相互作用。在这项工作中，利用蛋白质-蛋白质相互作用（PPI）数据库中的可用信息，为四种真核生物设计了烯醇化酶PPI网络，这四种真核生物分别是人、黑腹果蝇、秀丽隐杆线虫和酿酒酵母，涵盖了生命这个领域的广泛范围。生成了节点数从140到411且连接数多达15855的PPI网络，并对所有网络进行了模块化和中心性分析以及功能富集分析。所进行的分析表明，烯醇化酶是网络中的中心节点，并且除了与糖酵解和能量代谢相关的蛋白质的典型相互作用外，它还是与不同生物过程（如转录、发育和细胞凋亡等）相关的蛋白质簇的一部分。其中一些非糖酵解簇在网络之间部分保守，体现在直系同源物的总体共享、总体簇结构和/或簇内关键调节蛋白的水平上。总体而言，我们的结果提供了烯醇化酶多功能性以及烯醇化酶PPI在所有这些水平上的进化保守性的证据。
