6bzh
From Proteopedia
Structure of mouse RIG-I tandem CARDs
Structural highlights
FunctionRIGI_MOUSE Innate immune receptor that senses cytoplasmic viral nucleic acids and activates a downstream signaling cascade leading to the production of type I interferons and pro-inflammatory cytokines. Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments. The homooligomerization allows the recruitment of RNF135 an E3 ubiquitin-protein ligase that activates and amplifies the RIG-I-mediated antiviral signaling in an RNA length-dependent manner through ubiquitination-dependent and -independent mechanisms. Upon activation, associates with mitochondria antiviral signaling protein (MAVS/IPS1) that activates the IKK-related kinases TBK1 and IKBKE which in turn phosphorylate the interferon regulatory factors IRF3 and IRF7, activating transcription of antiviral immunological genes including the IFN-alpha and IFN-beta interferons. 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. Detects both positive and negative strand RNA viruses including members of the families Paramyxoviridae: Sendai virus (SeV), Rhabdoviridae and Flaviviridae. It also detects rotavirus and orthoreovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome. Detects dsRNA produced from non-self dsDNA by RNA polymerase III. 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
| ||||||||||||||||||||
