Figure 5.
Cartoon representations of RIG-I autoimmune signaling events. In the resting state, RIG-I adopts an autoinhibited conformation via CARD2-HEL2i interaction. RIG-I can recognize nonself RNA and discriminate against self RNA, resulting in distinguished CARDs opening events. Unlike WT RIG-I, apo RIG-IE510V and apo RIG-IQ517H are coupled with a reduced gradient of CARD2-HEL2i engagement. RIG-IE510V can distinguish self from nonself RNA via its HEL-CTD module and activate CARDs differently but to lesser extents than RIG-I. RIG-IQ517H, however, fails to distinguish self from nonself RNA and results in fast CARDs unfolding events at similar unfolding rates. The subsequent K63-polyUb9 can bind to activated CARDs and trigger CARDs oligomerizations prior to MAVS activation.