Investigating The Interaction Between TRIM25 And RIG-? By NMR

RIG-? is an important member of cellular pattern recognition receptors in the innate immune system.When exogenous viral RNA enters the cell,RIG-? is activated from the self-inhibition state by recognizing the viral RNA with the exposure of two N-terminal tandem caspase activation and recruitment domains(CARDs)for interaction with downstream molecules.TRIM25 is an important regulator of RIG-?.The C-terminal PRYSPRY domain of TRIM25 binds to the exposed CARDs domain,and its N-terminal RING domain can transfer ubiquitin to the CARDs leading to the oligomerization of RIG-? and the downstream MAYS on mitochondria to activate the signaling pathway,which leads to the production of type ? interferon to counter the viral invasion.Besides the antiviral innate immune signaling pathway,TRIM25,as one of the important members of the TRIM family,also plays important roles in the cell proliferation and development,as well as cancer.In this thesis,the interaction between PRYSPRY domain of TRIM25 was investigated.The 15N-labeled PRYSPRY and CARDs domains were expressed,and purified in E.coli.The interacting residues were determined by nuclear magnetic resonance,and the resulting interacting model was verified by cell-based methods,which contributes important structural data to the field.