The structural basis of 5' triphosphate double-stranded RNA recognition by RIG-I C-terminal domain.

Publication Type:

Journal Article


Structure (London, England : 1993), Volume 18, Issue 8, p.1032-43 (2010)


2010, Base Sequence, Basic Sciences Division, Center-Authored Paper, Chromatography, Gel, Crystallography, X-Ray, DEAD-box RNA Helicases, Electrophoretic Mobility Shift Assay, Escherichia coli, Humans, Models, Molecular, Molecular Sequence Data, mutagenesis, Polyphosphates, Protein Binding, Protein Conformation, RNA, Double-Stranded, Sequence Analysis, DNA, Surface Plasmon Resonance, Ultracentrifugation


RIG-I is a cytosolic sensor of viral RNA that plays crucial roles in the induction of type I interferons. The C-terminal domain (CTD) of RIG-I is responsible for the recognition of viral RNA with 5' triphosphate (ppp). However, the mechanism of viral RNA recognition by RIG-I is still not fully understood. Here, we show that RIG-I CTD binds 5' ppp dsRNA or ssRNA, as well as blunt-ended dsRNA, and exhibits the highest affinity for 5' ppp dsRNA. Crystal structures of RIG-I CTD bound to 5' ppp dsRNA with GC- and AU-rich sequences revealed that RIG-I recognizes the termini of the dsRNA and interacts with the 5' ppp through extensive electrostatic interactions. Mutagenesis and RNA-binding studies demonstrated that similar binding surfaces are involved in the recognition of different forms of RNA. Mutations of key residues at the RNA-binding surface affected RIG-I signaling in cells.