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PMID:20581823
Citation |
Wang, Y, Ludwig, J, Schuberth, C, Goldeck, M, Schlee, M, Li, H, Juranek, S, Sheng, G, Micura, R, Tuschl, T, Hartmann, G and Patel, DJ (2010) Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I. Nat. Struct. Mol. Biol. 17:781-7 |
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Abstract |
RIG-I is a cytosolic helicase that senses 5'-ppp RNA contained in negative-strand RNA viruses and triggers innate antiviral immune responses. Calorimetric binding studies established that the RIG-I C-terminal regulatory domain (CTD) binds to blunt-end double-stranded 5'-ppp RNA a factor of 17 more tightly than to its single-stranded counterpart. Here we report on the crystal structure of RIG-I CTD bound to both blunt ends of a self-complementary 5'-ppp dsRNA 12-mer, with interactions involving 5'-pp clearly visible in the complex. The structure, supported by mutation studies, defines how a lysine-rich basic cleft within the RIG-I CTD sequesters the observable 5'-pp of the bound RNA, with a stacked phenylalanine capping the terminal base pair. Key intermolecular interactions observed in the crystalline state are retained in the complex of 5'-ppp dsRNA 24-mer and full-length RIG-I under in vivo conditions, as evaluated from the impact of binding pocket RIG-I mutations and 2'-OCH(3) RNA modifications on the interferon response. |
Links |
PubMed PMC3744876 Online version:10.1038/nsmb.1863 |
Keywords |
Amino Acid Sequence; Binding Sites; Crystallography, X-Ray; DEAD Box Protein 58; DEAD-box RNA Helicases/chemistry; DEAD-box RNA Helicases/genetics; DEAD-box RNA Helicases/immunology; DEAD-box RNA Helicases/metabolism; Humans; Immunity, Innate; Interferon-Induced Helicase, IFIH1; Models, Molecular; Molecular Sequence Data; Nucleic Acid Conformation; Point Mutation; Protein Binding; Protein Conformation; Protein Structure, Tertiary; RNA Helicases/chemistry; RNA Helicases/metabolism; RNA, Double-Stranded/chemistry; RNA, Double-Stranded/metabolism; Sequence Alignment |
Significance
Annotations
Gene product | Qualifier | GO Term | Evidence Code | with/from | Aspect | Extension | Notes | Status |
---|---|---|---|---|---|---|---|---|
enables |
GO:0042802: identical protein binding |
ECO:0000353: physical interaction evidence used in manual assertion |
UniProtKB:O95786-1 |
F |
Seeded From UniProt |
complete | ||
Notes
See also
References
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