Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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DEAD Box Protein 58
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DEAD-box RNA Helicases / chemistry
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DEAD-box RNA Helicases / genetics
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DEAD-box RNA Helicases / metabolism*
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Gene Expression Regulation
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Humans
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Immune System / physiology*
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Interferon Regulatory Factor-3 / chemistry
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Interferon Regulatory Factor-3 / genetics
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Interferon Regulatory Factor-3 / metabolism
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Interferons / immunology
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Mice
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Mice, Knockout
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Models, Molecular
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Molecular Sequence Data
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Nuclear Magnetic Resonance, Biomolecular
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Nucleic Acid Conformation*
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Oligonucleotides / chemistry
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Oligonucleotides / genetics
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Oligonucleotides / immunology
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Protein Binding
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Protein Conformation
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Protein Structure, Tertiary
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RNA, Double-Stranded / chemistry
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RNA, Double-Stranded / genetics
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RNA, Double-Stranded / immunology
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RNA, Viral / chemistry*
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RNA, Viral / genetics
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RNA, Viral / immunology*
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Sequence Alignment
Substances
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Interferon Regulatory Factor-3
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Oligonucleotides
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RNA, Double-Stranded
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RNA, Viral
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Interferons
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DDX58 protein, human
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DEAD Box Protein 58
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DEAD-box RNA Helicases