Figure 2.

RIG-I-like receptor signaling pathway. The three human RIG-I-like receptors RIG-I, MDA5, and LGP2 detect foreign cytosolic double-stranded (ds) RNA, as for example released from entering RNA viruses, and induce an immune response to fight off the infection. In the absence of RNA ligands, signaling by RIG-I and MDA5 is prevented by shielding 2CARD from cytosolic interaction partners. 1, upon RNA detection both RIG-I and MDA5 release their 2CARD signaling module. RIG-I preferentially binds to nonmethylated dsRNA ends containing 5′-tri- or -diphosphates and further needs ATP to eject 2CARD. MDA5, in contrast, cooperatively binds to long dsRNA and forms filaments that are probably stabilized or seeded by LGP2. 2, each four released 2CARD modules of RIG-I or MDA5 subsequently assemble into tetramers and are stabilized by polyubiquitination or ubiquitin binding. 3, RLR 2CARD tetramerization, in turn, triggers the oligomerization of the RLR adapter protein MAVS. MAVS is distributed on the outer mitochondrial membrane but polymerizes into long filaments if seeded by 2CARD protomers. 4, this brings together many interaction sites of downstream factors within the MAVS unstructured region and activates a signaling cascade that leads to the expression of type I interferons or other cytokines and sets the cell into an antiviral state.