Date of Award
Bachelor of Science
Tank Binding Kinase 1 (TBK1) acts as a catalytic hub in the regulation of numerous immune signaling pathways. Suppressor of IκB Kinase ε (SIKE) was recently characterized as a substrate of TBK1 whose binding properties are modulated by phosphorylation state, but very little is currently known about its function. However, because SIKE is known to form a dimer with itself, previous work generated a list of potential SIKE partners based on other proteins that contain sequences homologous to SIKE. Here, computational models of four potential SIKE partners, Heavy Chain myosin, tubulin, Beta Catenin and Ezrin, were generated and docked with SIKE in order to predict their possible mechanisms of interaction. These models revealed that theoretical interactions between SIKE and all four of these partners bear significant resemblance to the modeled interactions between SIKE and itself, supporting the conclusion that SIKE is likely to interact with these partners. Furthermore, analysis of the phosphorylation sites on SIKE demonstrated that they were all located very far from the interaction sites in three-dimensional space. Together, these results suggest that the three-dimensional conformation of SIKE is altered based on its phosphorylation state, and that SIKE may be activated by TBK1 signaling in order to regulate the cytoskeleton in response to immune challenges.
Catalano, John, "Understanding the structural basis of SIKE interactions" (2018). Honors Theses. 1304.