Structural and functional insights into 5′-ppp RNA pattern recognition by the innate immune receptor RIG-I Journal Article
| Authors: | Ludwig, J.; Schuberth, C.; Goldeck, M.; Schlee, M.; Li, H.; Juranek, S.; Sheng, G.; Micura, R.; Tuschl, T.; Hartmann, G.; Patel, D. J.; Wang, Y. |
| Article Title: | Structural and functional insights into 5′-ppp RNA pattern recognition by the innate immune receptor RIG-I |
| 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. © 2010 Nature America, Inc. All rights reserved. |
| Keywords: | controlled study; protein expression; human cell; binding affinity; protein conformation; carboxy terminal sequence; protein binding; in vivo study; enzyme linked immunosorbent assay; dead-box rna helicases; amino acid sequence; molecular sequence data; sequence alignment; rna viruses; immunity, innate; base pairing; crystal structure; models, molecular; crystallography, x-ray; protein structure, tertiary; binding sites; conformational transition; nucleic acid conformation; rna structure; point mutation; cell stimulation; gel mobility shift assay; rna helicases; phenylalanine; double stranded rna; complementary rna; rna, double-stranded; retinoic acid inducible protein i; single stranded rna; pattern recognition |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 17 |
| Issue: | 7 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2010-07-01 |
| Start Page: | 781 |
| End Page: | 787 |
| Language: | English |
| DOI: | 10.1038/nsmb.1863 |
| PUBMED: | 20581823 |
| PROVIDER: | scopus |
| PMCID: | PMC3744876 |
| DOI/URL: | |
| Notes: | --- - "Cited By (since 1996): 5" - "Export Date: 20 April 2011" - "CODEN: NSMBC" - "Source: Scopus" |
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