Visualizing the determinants of viral RNA recognition by innate immune sensor RIG-I

By Dahai Luo, Andrew S. Kohlway, Adriana Vela, A. Pyle. 2012

80 citations recorded by the source corpus.

Summary 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′tri-phosphorylated RNA hairpin and ADP nucleotide at 2.8Å 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, semi-closed 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.

Subfields: Immunology, Molecular Biology

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Citations in the corpus

The RIG-I receptor adopts two different conformations for distinguishing host from viral RNA ligands (2022, neutral): “6 Molecular Cell 82, 1–14, November 3, 2022 graphic investigation of this complex (Figures 3E and 3F) (Luo et al., 2012).”
Establishing the role of ATP for the function of the RIG-I innate immune sensor (2015, background): “DOI: 10.7554/eLife.09391 11 of 21 derives from a complex network of specific interactions with the 5′ triphosphate moiety and stacking interactions with the terminal base pair of an RNA duplex (Lu et al., 2010; Jiang et al., 2011; Kowalinski et al., 2011; Luo et al., 2011, 2012b).”
A minimal RNA ligand for potent RIG-I activation in living mice (2017, background): “RESULTS SLRs are an optimal design for RIG-I recognition Unlike other RNAmolecules that have been developed as RIG-I activators, complexes between SLRs and RIG-I molecules have been characterized crystallographically (3, 10, 23), making it possible to visualize and optimize the molecular interaction”
Defining the functional determinants for RNA surveillance by RIG-I (2013, unknown): “changes in the ATP-binding pocket among the conformations, including movements of the phosphate-binding loop and K270 of motif I, suggesting that the pincer and HEL2i motions might be linked to ATP-binding and hydrolysis (Fig 1D) [29].”
Cytosolic Sensing of Viruses (2013, background): “At the same time, the helicase domain binds to the duplexed-RNA sugarphosphate backbone in a ring-shaped clamp, which is further compacted upon ATP hydrolysis (Jiang et al., 2011a; Kowalinski et al., 2011; Luo et al., 2012).”
A structure-based model of RIG-I activation. (2012, background): “This review focuses on RIG-I and the new insight that a series of high-resolution crystal structures provide about how RIG-I is activated upon detecting and binding a certain class of viral RNAs (Civril et al. 2011; Jiang et al. 2011; Kowalinski et al. 2011; Luo et al. 2011, 2012).”
Structural basis for m7G recognition and 2′-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I (2016, unknown): “This interaction was reported in the structure of RD with 5′ppp 14bp dsRNA (PDB ID 3LRN) (6, 7, 16).”
An evolving arsenal: viral RNA detection by RIG-I-like receptors (2014, background): “In RIG-I, the CTD has evolved to engage in a high affinity interaction with a triphosphate group [13, 17, 18 ] present at the dsRNA termini of deposited genomic RNA [19, 20] or replicative intermediates [21] of target viruses (Figure 1 Detection).”