Preliminary results from structural systems biology approach in Tetrahymena thermophila reveal novel perspectives for th
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ORIGINAL PAPER
Preliminary results from structural systems biology approach in Tetrahymena thermophila reveal novel perspectives for this toxicological model Christos T. Chasapis1 Received: 16 July 2018 / Revised: 28 August 2018 / Accepted: 5 September 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018
Abstract Tetrahymena is a unicellular microbial eukaryotic organism that has been used extensively in toxicology and environmental research. This work attempts to model for the first time the wiring of proteins involved in cellular mechanisms of Cd toxicity in Tetrahymena thermophila. 1975 high-confidence PPIs between 68 Cd-binding proteins and 422 partners were inferred through a novel structural systems biology approach that utilizes comparative analysis between Tetrahymena and other eukaryotes for which experimentally supported protein interactomes exist. The PPIs of the potential network were confirmed by known domain interactions in the Protein Data Bank and its topological characteristics were compared with publicly available experimental information for T. thermophila. To experimentally validate the robustness of the proposed PPI network, the interaction between the two most interconnected hub proteins was detected through GST pull-down assay. Potential effects on Tetrahymena’s cellular and metabolic processes by PPIs involving Cd-binding proteins were uncovered. Furthermore, 244 PPIs in which Cd-binding proteins or/and their partners are encoded by orthologs of human disease genes in T. thermophila, but not in yeast, were identified and analyzed. The findings suggest that Tetrahymena could be possibly a useful model for an improved understanding of molecular mechanisms of Cd toxicity in human diseases. Keywords Protozoa · Tetrahymena · Cd toxicity · Metalloproteins · PPI network · Structural systems biology
Introduction The ciliated protozoa Tetrahymena has been used in toxicology (Loutsidou et al. 2012; Stefanidou et al. 2011; Vasia Hatzi et al. 2011), for decades as a useful model organism for cellular and molecular biologists as well as for environmental research (Amaro et al. 2011, 2014; Barchetta et al. 2005). It is also an advantageous eukaryotic model system for mechanistic studies, as it contains many genes conserved
Communicated by Erko Stackebrandt. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00203-018-1571-6) contains supplementary material, which is available to authorized users. * Christos T. Chasapis [email protected] 1
Institute of Chemical Engineering Sciences, Foundation for Research and Technology-Hellas (FORTH/ICE-HT), 26504 Patras, Greece
in several eukaryotes (including humans), differently from other widely used unicellular model organisms. For instance, more than 800 human genes have orthologs in Tetrahymena thermophila but not in S. cerevisiae, and 58 of these genes are associated with human diseases (Eisen et al. 2006). Many metals play important roles in all the organisms across the three kingdoms of
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