Anti-cooperative and cooperative protein-protein interactions between TetR isoforms on synthetic enhancers.
Protein-protein interactions play an important role in determining the regulatory output of cis regulatory regions. In this work, we revisit the regulatory output functions recorded for the synthetic enhancers that contain binding sites for TetR. We use our thermodynamic model as an analysis tool to infer that two different types of interactions may take place between the TetR molecules. First, a strong mutually exclusive anti-cooperative interaction precludes the synthetic enhancer from being occupied by more than one AT (the aTc bound TetR isoform) protein, and a second weak cooperative interaction exists between the aTc-free TetR isoform (T). Consequently, this work highlights the power of the synthetic enhancer approach as a tool for studying protein-protein interactions via an experimentally verifiable prediction for the general mode of binding of the TetR repressor.
Department of Biotechnology and Food Engineering, Technion-Israel Institute of Technology, Haifa, Israel. roeeamit@technion.ac.il
Roee
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Amit
D000465:Algorithms; D003198:Computer Simulation; D004269:DNA, Bacterial / Q000235:genetics; D004742:Enhancer Elements, Genetic; D029968:Escherichia coli Proteins / Q000235:genetics; D015964:Gene Expression Regulation, Bacterial; D008957:Models, Genetic; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics; D058615:Synthetic Biology; D013753:Tetracycline Resistance / Q000235:genetics; D013816:Thermodynamics
D004269:DNA, Bacterial; D029968:Escherichia coli Proteins; D020033:Protein Isoforms