Figure 1.

Schematic representation of structural rearrangements of RIG-I upon binding distinct types of RNA. (a) Conformational changes and domain rearrangements that RIG-I can undergo when binding RNA. All RNA binding leads to the ejection of the N-terminal CARDs, independent of nucleotide presence. Top panel: Binding of short 5′-triphosphate dsRNA leads to rearrangement of the helicase core, an unstructured HEL_TNT loop (sequence N₆₆₄-RGKTNQNTG-C₆₇₂), and a CTD orientation that caps the 5′-end of RNA. Middle panel: Binding of short dsRNA ending with a 5′-hydroxy group leads to rearrangement of the helicase core, a structured HEL_TNT loop, and a CTD orientation that caps the 5′-end of RNA. Bottom panel: Binding of long dsRNA (here 112 bp) leads to rearrangement of the helicase core, a structured HEL_TNT loop, and the CTD rotated away from the central axis of RNA as in the case of MDA5. (b) Cartoon representation of differences seen for the CTD and HEL_TNT loop conformations when binding the respective types of RNA. The CTD is represented as a gray sphere, and short versus long RNA are color-coded black and blue, respectively. The apparent displacement of the CTD upon binding long RNA can be observed (bottom panel). The HEL_TNT loop is indicated in teal, and it is disordered when short 5′-triphosphate is bound to RIG-I (top panel); in the presence of short RNA ending with 5′-hydroxy group (middle panel) or long RNA (bottom panel), the loop becomes structured. CARDs: caspase activation and recruitment domains; CTD: C-terminal domain; dsRNA: double-stranded RNA; MDA5: melanoma differentiation-associated gene 5; RIG-I: retinoic acid-inducible gene I.