Structural and Functional Analysis of RIG-I Like Helicases -

TL;DRAbstract

The cytosolic helicases RIG-I and MDA5 are primary sensors for viral RNA during infection. Although their overall role as key players in the antiviral response and the induced signaling pathways have been elucidated in great detail over the past years, a structural and functional understanding of virus recognition by these sensors is missing. On the basis of an X-ray structure of RIG-I RD the 5’-triphosphate interaction site could be mapped to a previously identified positively charged groove. Structural modeling of the homologous RD of MDA5 gave a rational for its lower affinity to RNA. Based on a comparison of enzymatic activities of several RIG-I truncation variants, a model for the transition from the inactive to the active state was postulated. In contrast to RIG-I, the molecular patterns which lead to MDA5-dependent anti-viral signaling are still insufficiently understood. Here it is shown that the dsRNA-mimic poly I:C is a potent activator of MDA5 ATPase activity in vitro. The A

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