Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses.
A DExD/H protein, RIG-I, is critical in innate antiviral responses by sensing viral RNA. Here we show that RIG-I recognizes two distinct viral RNA patterns: double-stranded (ds) and 5'ppp single-stranded (ss) RNA. The binding of RIG-I with dsRNA or 5'ppp ssRNA in the presence of ATP produces a common structure, as suggested by protease digestion. Further analyses demonstrated that the C-terminal domain of RIG-I (CTD) recognizes these RNA patterns and CTD coincides with the autorepression domain. Structural analysis of CTD by NMR spectroscopy in conjunction with mutagenesis revealed that the basic surface of CTD with a characteristic cleft interacts with RIG-I ligands. Our results suggest that the bipartite structure of CTD regulates RIG-I on encountering viral RNA patterns.
Takahasi
Kiyohiro
K
Department of Structural Biology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Hokkaido 060-0812, Japan.
Yoneyama
Mitsutoshi
M
Nishihori
Tatsuya
T
Hirai
Reiko
R
Kumeta
Hiroyuki
H
Narita
Ryo
R
Gale
Michael
M
Inagaki
Fuyuhiko
F
Fujita
Takashi
T
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007107:Immune System / Q000502:physiology*; D050838:Interferon Regulatory Factor-3 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D007372:Interferons / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D012367:RNA, Viral / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D011971:Receptors, Immunologic; D016415:Sequence Alignment
D050838:Interferon Regulatory Factor-3; D009841:Oligonucleotides; D012330:RNA, Double-Stranded; D012367:RNA, Viral; D011971:Receptors, Immunologic; D007372:Interferons; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases