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Date of Award
Restricted Thesis: Campus only access
Bachelor of Science
Biochemistry & Molecular Biol.
Dr. Ellis Bell
In the toll-like receptor 3 (TLR3) innate immune system pathway, TANK-binding kinase 1 (TBK1) serves as an essential regulator of inflammatory mediators that has the ability to regulate type-I interferons via phosphorylation of interferon regulatory factor 3 (IRF3). Previous studies have shown that suppressor of IKKε (SIKE) functions as a mixed- type inhibitor of TBK1 by acting as a high affinity substrate. However, little is known about the structure or the function of SIKE despite its relevance to the regulation of TBK1. Due to SIKE’s inability to form a crystal or display a pertinent 2D NMR spectrum, potential structures and functions of SIKE were obtained computationally from sequence-based homology modeling. Secondary structure of SIKE was investigated with circular dichroism, and the SIKE sequence was used to perform disordered region predictions. Fluorescence thermal shift assay, fluorescence polarization, and hydrogen-deuterium exchange experiments were conducted to support the predictions made from the SIKE sequence and the homology models. Results suggest that SIKE is an open, predominantly alpha helical protein that contains several regions of intrinsic disorder that may form stable helical structure. SIKE also appears to be capable of binding select divalent medal ions and forming at least a homodimer.
Kim, Seung-Hwan L., "Analysis of SIKE Structure" (2017). Honors Theses. 994.