Preliminary results from structural systems biology approach in Tetrahymena thermophila reveal novel perspectives for this toxicological model

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.