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2rmj
From Proteopedia
Solution structure of RIG-I C-terminal domain
Structural highlights
Function[DDX58_HUMAN] Innate immune receptor which acts as a cytoplasmic sensor of viral nucleic acids and plays a major role in sensing viral infection and in the activation of a cascade of antiviral responses including the induction of type I interferons and proinflammatory cytokines. Its ligands include: 5'-triphosphorylated ssRNA and dsRNA and short dsRNA (<1 kb in length). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential. Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity. A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity. Upon ligand binding it associates with mitochondria antiviral signaling protein (MAVS/IPS1) which activates the IKK-related kinases: TBK1 and IKBKE which phosphorylate interferon regulatory factors: IRF3 and IRF7 which in turn activate transcription of antiviral immunological genes, including interferons (IFNs); IFN-alpha and IFN-beta. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Human respiratory syncytial virus and measles virus (MeV), Rhabdoviridae: vesicular stomatitis virus (VSV), Orthomyxoviridae: influenza A and B virus, Flaviviridae: Japanese encephalitis virus (JEV), hepatitis C virus (HCV), dengue virus (DENV) and west Nile virus (WNV). It also detects rotavirus and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV). Detects dsRNA produced from non-self dsDNA by RNA polymerase III, such as Epstein-Barr virus-encoded RNAs (EBERs). May play important roles in granulocyte production and differentiation, bacterial phagocytosis and in the regulation of cell migration.[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedA 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. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses.,Takahasi K, Yoneyama M, Nishihori T, Hirai R, Kumeta H, Narita R, Gale M Jr, Inagaki F, Fujita T Mol Cell. 2008 Feb 29;29(4):428-40. Epub 2008 Jan 31. PMID:18242112[14] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Human | Fujita, T | Gale, M | Hirai, R | Inagaki, F | Narita, R | Nihishori, T | Takahasi, K | Yoneyama, M | Alternative splicing | Antiviral defense | Atp-binding | Cytoplasm | Helicase | Hydrolase | Immune response | Innate immunity | Interferon induction | Nucleotide-binding | Polymorphism | Rna binding protein | Rna-binding | Ubl conjugation
