Molecular imprinting as a signal activation mechanism of the viral RNA sensor RIG-I

Summary RIG-I activates interferon signaling pathways by promoting filament formation of the adaptor molecule, MAVS. Assembly of the MAVS filament is mediated by its CARD domain (CARD MAVS ), and requires its interaction with the tandem CARDs of RIG-I (2CARD RIG-I ). However, the precise nature of the interaction between 2CARD RIG-I and CARD MAVS , and how this interaction leads to CARD MAVS filament assembly, has been unclear. Here we report a 3.6 A electron microscopy structure of the CARD MAVS  filament and a 3.4 A crystal structure of the 2CARD RIG-I :CARD MAVS complex, representing 2CARD RIG-I "caught in the act" of nucleating the CARD MAVS filament. These structures, together with functional analyses, show that 2CARD RIG-I acts as a template for the CARD MAVS filament assembly, by forming a helical tetrameric structure and recruiting CARD MAVS along its helical trajectory. Our work thus reveals that signal activation by RIG-I occurs by imprinting its helical assembly architecture on MAVS, a previously uncharacterized mechanism of signal transmission.