Retinoic acid inducible gene-I (RIG-I) is a key intra- cellular immune receptor for pathogenic RNAs, particularly from RNA viruses. Here, we report the crystal structure of human RIG-I bound to a 50
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 acti- vation upon viral infection.
INTRODUCTION
Pathogen recognition receptors (PRRs) are signaling proteins
that continually survey cells for the presence of pathogen associ-
ated molecular patterns (PAMPs). Retinoic acid inducible gene I
(RIG-I) is a major cellular PRR that senses viral RNA PAMPs in
the cytoplasm of infected cells (Kato et al., 2011; Yoneyama
et al., 2004). RIG-I recognizes a broad spectrum of viruses,
including the negative-stranded vesicular stomatitis virus, influ-
enza, and rabies viruses, and also positive-stranded viruses
such as dengue and hepatitis C virus (Kawai and Akira, 2007;
Ramos and Gale, 2011). Defective viral replication by Sendai
virus and influenza virus generates short subgenomic RNAs
that may be a principal ligand for RIG-I during viral infection
(BaumandGarcı́a-Sastre, 2011;Baumet al., 2011). At themolec-
ular level, RIG-I preferentially recognizes double stranded RNAs
that contain a triphosphate moiety at the 50 end, exemplified by thepanhandle-likeRNAsof negative-strand viruses such as influ-
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