title: Systems biology approach reveals possible evolutionarily conserved moonlighting functions for enolase.
abstract: 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.
authors.affiliation: Laboratório de Genômica Estrutural e Funcional, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
authors.forename: Gabriela Prado
authors.initials: GP
authors.lastname: Paludo
authors.affiliation: 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.
authors.forename: Karina Rodrigues
authors.initials: KR
authors.lastname: Lorenzatto
authors.affiliation: Laboratório de Radiobiologia Molecular, Centro de Biotecnologia, UFRGS, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, UFRGS, Porto Alegre, RS, Brazil; Departamento de Biologia Molecular e Biotecnologia, Instituto de Biociências, UFRGS, Porto Alegre, RS, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Bonatto
authors.affiliation: 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; Departamento de Biologia Molecular e Biotecnologia, Instituto de Biociências, UFRGS, Porto Alegre, RS, Brazil. Electronic address: henrique@cbiot.ufrgs.br.
authors.forename: Henrique Bunselmeyer
authors.initials: HB
authors.lastname: Ferreira
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D019143:Evolution, Molecular; D006801:Humans; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D012441:Saccharomyces cerevisiae; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D049490:Systems Biology
chemical_list: D029742:Caenorhabditis elegans Proteins; D029721:Drosophila Proteins; D029701:Saccharomyces cerevisiae Proteins; D010751:Phosphopyruvate Hydratase
keywords: Enolase; Glycolytic enzyme; Moonlighting functions; Protein–protein interaction network; Systems biology