Physical Sciences and Mathematics Commons^™

Using Structural Analysis To Investigate The Function Of Suppressor Of Ikk-Epsilon (Sike), Sean W. Mckinley

Theses and Dissertations

The innate immune system provides the body’s first line of defense against pathogenic challenge through pathogen recognition and initiation of the immune response. Among the various cellular mechanisms of pathogen recognition in mammals, Toll-like receptor 3 (TLR3) recognizes viral dsRNA. Stimulation of TLR3 signaling pathway leads to transcription of pro-inflammatory cytokines and type-1 Interferons. Suppressor of IKKε (SIKE) interacts with two kinases in the signaling pathway, IKKε and TANK binding kinase 1 (TBK1), inhibiting the transcription of type I interferons. Recently, the Bell Laboratory discovered that SIKE blocks TBK1-mediated activation of type I interferons by acting as a high affinity, …