Structural and functional studies on vaccinia virus E3 protein
Abstract
E3 protein from vaccinia virus is a key host-range protein, which suppresses the innate antiviral immune response of the infected cells. In response to the viral infection, Protein Kinase R (PKR) of the host cell initiates the immune response via a cascade of reactions. E3 attacks PKR to suppress the immune response, but the mechanism of PKR inhibition by E3 is unknown. In this study, it was found that the kinase domain of PKR had a physical interaction with E3 that has biochemical relevance. E3 follows two different pathways when inhibiting inactivated and activated PKR-KD. E3 binds to monomeric PKR-KD inhibiting its phosphorylation by forming an inactive heterodimer, which eventually leads to disruption of immune response via PKR in host cells. The mechanism of E3 inhibition of dimeric PKR-KD is unknown but the data suggests a weak interaction between the proteins leading to disruption of PKR activity. The study also detailed the importance of both N and C terminals of E3 for PKR inhibition. Further analysis of the interaction revealed that the inhibition of PKR-KD activation by E3 protein does not correlate with the dsRNA binding ability of PKR or E3.
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- OSU Dissertations [11222]