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| - | {{STRUCTURE_3zd6| PDB=3zd6 | SCENE= }}
| + | ==Snapshot 1 of RIG-I scanning on RNA duplex== |
| - | ===Snapshot 1 of RIG-I scanning on RNA duplex===
| + | <StructureSection load='3zd6' size='340' side='right' caption='[[3zd6]], [[Resolution|resolution]] 2.80Å' scene=''> |
| - | {{ABSTRACT_PUBMED_23897087}}
| + | == Structural highlights == |
| | + | <table><tr><td colspan='2'>[[3zd6]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZD6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZD6 FirstGlance]. <br> |
| | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| | + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zd7|3zd7]]</td></tr> |
| | + | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/RNA_helicase RNA helicase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.4.13 3.6.4.13] </span></td></tr> |
| | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zd6 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zd6 RCSB], [http://www.ebi.ac.uk/pdbsum/3zd6 PDBsum]</span></td></tr> |
| | + | </table> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == 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. |
| | | | |
| - | ==Function==
| + | 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<ref>PMID:23897087</ref> |
| - | [[http://www.uniprot.org/uniprot/DDX58_HUMAN 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.<ref>PMID:15208624</ref> <ref>PMID:16125763</ref> <ref>PMID:15708988</ref> <ref>PMID:16153868</ref> <ref>PMID:16127453</ref> <ref>PMID:17190814</ref> <ref>PMID:18636086</ref> <ref>PMID:19631370</ref> <ref>PMID:19576794</ref> <ref>PMID:19122199</ref> <ref>PMID:19211564</ref> <ref>PMID:19609254</ref> <ref>PMID:21742966</ref>
| + | |
| | | | |
| - | ==About this Structure==
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| - | [[3zd6]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZD6 OCA].
| + | </div> |
| - | | + | == References == |
| - | ==Reference== | + | <references/> |
| - | <ref group="xtra">PMID:023897087</ref><references group="xtra"/><references/>
| + | __TOC__ |
| | + | </StructureSection> |
| | [[Category: Homo sapiens]] | | [[Category: Homo sapiens]] |
| | [[Category: RNA helicase]] | | [[Category: RNA helicase]] |
| - | [[Category: Luo, D.]] | + | [[Category: Luo, D]] |
| - | [[Category: Pyle, A M.]] | + | [[Category: Pyle, A M]] |
| | [[Category: Hydrolase-rna complex]] | | [[Category: Hydrolase-rna complex]] |
| | [[Category: Innate immunity]] | | [[Category: Innate immunity]] |
| Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kohlway A, Luo D, Rawling DC, Ding SC, Pyle AM. Defining the functional determinants for RNA surveillance by RIG-I. EMBO Rep. 2013 Jul 30. doi: 10.1038/embor.2013.108. PMID:23897087 doi:10.1038/embor.2013.108
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