Structural mechanism of the activation of RIG-I by viral RNA (A13)

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The ATPase RIG-I senses the presence of viral RNA in the cytoplasm and initiates a signal transduction cascade that leads to stimulation of the innate immune response. We have obtained first structural insights into recognition of viral RNA by RIG-I. In this proposal we want to derive a complete structural mechanism of activation of RIG-I by viral RNA. In collaboration we address by structural, biochemical and in vivo functional approaches, how RIG-I binds viral RNA and how RNA and ATP binding induce a signaling conformation in RIG-I that leads to stimulation of the innate immune response.