3zd6 | pdb_00003zd6

Snapshot 1 of RIG-I scanning on RNA duplex

spinqualitylabelsall models 3zd6, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3zd6 is a 3 chain structure with sequence from Homo sapiens and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Disease RIGI_HUMAN Singleton-Merten dysplasia. The disease is caused by variants affecting the gene represented in this entry. Function RIGI_HUMAN 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 (PubMed:15208624, PubMed:16125763, PubMed:15708988, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:29117565, PubMed:28469175, PubMed:31006531, PubMed:34935440). Forms a ribonucleoprotein complex with viral RNAs on which it homooligomerizes to form filaments (PubMed:15208624, PubMed:15708988). 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 (PubMed:28469175, PubMed:31006531). 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 (PubMed:28469175, PubMed:31006531). Ligands include 5'-triphosphorylated ssRNAs and dsRNAs but also short dsRNAs (<1 kb in length) (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). In addition to the 5'-triphosphate moiety, blunt-end base pairing at the 5'-end of the RNA is very essential (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). Overhangs at the non-triphosphorylated end of the dsRNA RNA have no major impact on its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). A 3'overhang at the 5'triphosphate end decreases and any 5'overhang at the 5' triphosphate end abolishes its activity (PubMed:15208624, PubMed:15708988, PubMed:19576794, PubMed:19609254, PubMed:21742966). 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) (PubMed:21616437, PubMed:21884169). It also detects rotaviruses and reoviruses (PubMed:21616437, PubMed:21884169). Detects and binds to SARS-CoV-2 RNAs which is inhibited by m6A RNA modifications (Ref.66). Also involved in antiviral signaling in response to viruses containing a dsDNA genome such as Epstein-Barr virus (EBV) (PubMed:19631370). 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. Publication Abstract from PubMed Retinoic acid-inducible gene-I (RIG-I) is an intracellular RNA sensor that activates the innate immune machinery in response to infection by RNA viruses. Here, we report the crystal structure of distinct conformations of a RIG-I:dsRNA complex, which shows that HEL2i-mediated scanning allows RIG-I to sense the length of RNA targets. To understand the implications of HEL2i scanning for catalytic activity and signalling by RIG-I, we examined its ATPase activity when stimulated by duplex RNAs of varying lengths and 5' composition. We identified a minimal RNA duplex that binds one RIG-I molecule, stimulates robust ATPase activity, and elicits a RIG-I-mediated interferon response in cells. Our results reveal that the minimal functional unit of the RIG-I:RNA complex is a monomer that binds at the terminus of a duplex RNA substrate. This behaviour is markedly different from the RIG-I paralog melanoma differentiation-associated gene 5 (MDA5), which forms cooperative filaments. Defining the functional determinants for RNA surveillance by RIG-I.,Kohlway A, Luo D, Rawling DC, Ding SC, Pyle AM EMBO Rep. 2013 Jul 30. doi: 10.1038/embor.2013.108. PMID:23897087 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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