6bzh
From Proteopedia
Structure of mouse RIG-I tandem CARDs
Structural highlights
Function[DDX58_MOUSE] 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: newcastle disease virus (NDV) and Sendai virus (SeV), 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 orthoreovirus. 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] Publication Abstract from PubMedThe retinoic acid-inducible gene-I (RIG-I) receptor recognizes short 5'-di and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as influenza A, ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the tripartite motif 25 (TRIM25) B30.2 protein-interaction domain. Here we present a novel second RIG-I-binding interface on the TRIM25 B30.2 domain that interacts with CARD1 and CARD2 of RIG-I and is revealed by removal of an N-terminal alpha-helix that mimics dimerization of the full-length protein. Further characterization of the TRIM25 coiled-coil and B30.2 regions indicated that the B30.2 domains move freely on a flexible tether, facilitating RIG-I CARD recruitment. The identification of a dual binding mode for the TRIM25 B30.2 domain is a first for the SPRY/B30.2 domain family and may be a feature of other SPRY/B30.2 family members. Identification of a second binding site on the TRIM25 B30.2 domain.,D'Cruz AA, Kershaw NJ, Hayman TJ, Linossi EM, Chiang JJ, Wang MK, Dagley LF, Kolesnik TB, Zhang JG, Masters SL, Griffin MD, Gack MU, Murphy JM, Nicola NA, Babon JJ, Nicholson SE Biochem J. 2017 Dec 19. pii: BCJ20170427. doi: 10.1042/BCJ20170427. PMID:29259080[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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