Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I

Retinoic acid inducible gene-I (RIG-I) is a key intracellular immune receptor for pathogenic RNAs, particularly from RNA viruses. Here, we report the crystal structure of human RIG-I bound to a 5′ triphosphorylated RNA hairpin and ADP nucleotide at 2.8 Å resolution. The RNA ligand contains all structural features that are essential for optimal recognition by RIG-I, as it mimics the panhandle-like signatures within the genome of negative-stranded RNA viruses. RIG-I adopts an intermediate, semiclosed conformation in this product state of ATP hydrolysis. The structure of this complex allows us to visualize the first steps in RIG-I recognition and activation upon viral infection. [Display omitted] ► Crystallographic structure of RIG-I with 5′ triphosphorylated RNA duplex and ADP ► Solution biophysical analysis of ATP-dependent RIG-I conformational change ► The structural basis for ATP-stimulated RIG-I activation RIG-I is a protein that serves as our first line of defense against RNA viruses by recognizing pathogenic RNA and initiating interferon response. Luo et al. provide the key molecular snapshot of an early stage of this process and establish the likely structural basis for ATP-stimulated RIG-I activation.