Lauren Sar
Mentors: Vanessa Gutierrez, PhD, Stacy Horner, PhD
The antiviral innate immune system is a vertebrate’s first line of defense against disease, sensing non-self patterns such as dsRNA and activating a larger immune response mediated by interferon. The two proteins RIG-I and 14-3-3ε are known to play a central role in this system. RIG-I is the molecule that senses dsRNA. RIG-I then binds to 14-3-3ε, which moves RIG-I to signal sites for a signal transduction cascade. This cascade leads to the production of interferon, beginning a wider antiviral response. The molecular mechanism by which these proteins interact is unknown. It is known that 14-3-3ε binds somewhere in RIG-I’s 2-CARD domains and that 14-3-3ε traditionally binds to post-translational modifications (PTMs). However, it does not bind to any PTMs in the 2-CARD. Interestingly, 14-3-3ε has a PTM, ufmylation, which is required for its’ interaction with RIG-I. The 2-CARD of RIG-I contains 2 LC3-interacting regions (LIRs), motifs known to interact with ufmylation. Here we investigate whether these LIR motifs mediate the binding of RIG-I and 14-3-3ε. Utilizing the expression of mutant plasmids with deletions of these LIRS, we show that both LIRS impact the interaction of RIG-I with 14-3-3ε.
