The Structure-basis Of RIG-I And TRIM25 Interaction

Innate immunity is the body’s first line of defense against pathogens.Being part of the innate immunity,RIG-I-mediated RLR antiviral signaling pathway plays an important role in the induction of type I interferon and the subsequent series of antiviral innate immune responses.After the recognition of short RNA ligands with the 5’-triphosphate cap,RIG-I undergoes conformational changes and oligomerization to launch the signaling pathway.This signaling process is under tight regulation through the post-translational modifications of RIG-I.E3 ligase TRIM25 is a key factor in controlling the RIG-I signaling by modifying RIG-I by the Lys63-linked ubiquitination.In this thesis,we aim to delineate the mechanism of TRIM25-mediated ubiquitination.We employed NMR methods to characterize the interaction between TRIM25 and RIG-I.By titration experiments,the amino acid residues important for the interaction were identified,which were verified by cell-based assays through mutations and immunoprecipitation.