Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I Dahai Luo,1,4 Andrew Kohlway,2 Adriana Vela,2 and Anna Marie Pyle1,3,4,* 1Department of Molecular, Cellular, and Developmental Biology 2Department of Molecular Biophysics and Biochemistry 3Department of Chemistry Yale University, New Haven, CT 06520, USA 4Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA

Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I Dahai Luo,1,4 Andrew Kohlway,2 Adriana Vela,2 and Anna Marie Pyle1,3,4,* 1Department of Molecular, Cellular, and Developmental Biology 2Department of Molecular Biophysics and Biochemistry 3Department of Chemistry Yale University, New Haven, CT 06520, USA 4Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA

*Correspondence: anna.pyle@yale.edu

http://dx.doi.org/10.1016/j.str.2012.08.029

SUMMARY

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

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The post Visualizing the Determinants of Viral RNA Recognition by Innate Immune Sensor RIG-I Dahai Luo,1,4 Andrew Kohlway,2 Adriana Vela,2 and Anna Marie Pyle1,3,4,* 1Department of Molecular, Cellular, and Developmental Biology 2Department of Molecular Biophysics and Biochemistry 3Department of Chemistry Yale University, New Haven, CT 06520, USA 4Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA appeared first on My Nursing Papers.

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