6gpg: Difference between revisions
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==Structure of the RIG-I Singleton-Merten syndrome variant C268F== | |||
<StructureSection load='6gpg' size='340' side='right' caption='[[6gpg]], [[Resolution|resolution]] 2.89Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[6gpg]] is a 3 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GPG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6GPG FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></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=6gpg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gpg OCA], [http://pdbe.org/6gpg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6gpg RCSB], [http://www.ebi.ac.uk/pdbsum/6gpg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6gpg ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[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> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The innate immune sensor RIG-I detects cytosolic viral RNA and requires a conformational change caused by both ATP and RNA binding to induce an active signalling state and to trigger an immune response. Previously, we showed that ATP hydrolysis removes RIG-I from lower affinity self-RNAs (Lassig et al., 2015), revealing how ATP turnover helps RIGI distinguish viral from self-RNA and explaining why a mutation in a motif that slows down ATP hydrolysis causes the autoimmune disease Singleton-Merten syndrome (SMS). Here we show that a different, mechanistically unexplained SMS variant, C268F, localised in the ATP binding P-loop, can signal independently of ATP but still dependent on RNA. The structure in complex with dsRNA reveals that C268F helps induce a similar structural conformation in RIG-I than ATP. Our results uncover an unexpected mechanism how a mutation in a P-loop ATPase can induce a gain-of-function ATP state in the absence of ATP. | |||
Unified mechanisms for self-RNA recognition by RIG-I Singleton-Merten syndrome variants.,Lassig C, Lammens K, Gorenflos Lopez JL, Michalski S, Fettscher O, Hopfner KP Elife. 2018 Jul 26;7. pii: 38958. doi: 10.7554/eLife.38958. PMID:30047865<ref>PMID:30047865</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 6gpg" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: RNA helicase]] | |||
[[Category: Hopfer, K P]] | |||
[[Category: Laessig, C]] | |||
[[Category: Lammens, K]] | |||
[[Category: Antiviral protein]] | |||
[[Category: Innate immune system]] | |||
[[Category: Rig-i]] | |||
[[Category: Rna binding protein]] | |||
[[Category: Rna-dependent atpase]] | |||
[[Category: Singleton-merten syndrome]] | |||