View source for 8g7v


==Cryo-EM structure of Riplet:RIG-I:dsRNA complex (end-inter)==
<StructureSection load='8g7v' size='340' side='right'caption='[[8g7v]], [[Resolution|resolution]] 3.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8g7v]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8G7V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8G7V FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.9&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GTP:GUANOSINE-5-TRIPHOSPHATE'>GTP</scene>, <scene name='pdbligand=UTP:URIDINE+5-TRIPHOSPHATE'>UTP</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8g7v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8g7v OCA], [https://pdbe.org/8g7v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8g7v RCSB], [https://www.ebi.ac.uk/pdbsum/8g7v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8g7v ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/RIGI_HUMAN RIGI_HUMAN] Singleton-Merten dysplasia. The disease is caused by variants affecting the gene represented in this entry.
== Function ==
[https://www.uniprot.org/uniprot/RIGI_HUMAN 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:15708988, PubMed:16125763, PubMed:16127453, PubMed:16153868, PubMed:17190814, PubMed:18636086, PubMed:19122199, PubMed:19211564, PubMed:24366338, PubMed:28469175, PubMed:29117565, PubMed:31006531, PubMed:34935440, PubMed:35263596, PubMed:36793726). 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.70). 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.<ref>PMID:15208624</ref> <ref>PMID:15708988</ref> <ref>PMID:16125763</ref> <ref>PMID:16127453</ref> <ref>PMID:16153868</ref> <ref>PMID:17190814</ref> <ref>PMID:18636086</ref> <ref>PMID:19122199</ref> <ref>PMID:19211564</ref> <ref>PMID:19576794</ref> <ref>PMID:19609254</ref> <ref>PMID:19631370</ref> <ref>PMID:21742966</ref> <ref>PMID:24366338</ref> <ref>PMID:28469175</ref> <ref>PMID:29117565</ref> <ref>PMID:31006531</ref> <ref>PMID:34935440</ref> <ref>PMID:35263596</ref> <ref>PMID:36793726</ref> [REFERENCE:70]<ref>PMID:21616437</ref> <ref>PMID:21884169</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
RIG-I is an essential innate immune receptor that responds to infection by RNA viruses. The RIG-I signaling cascade is mediated by a series of post-translational modifications, the most important of which is ubiquitination of the RIG-I Caspase Recruitment Domains (CARDs) by E3 ligase Riplet. This is required for interaction between RIG-I and its downstream adapter protein MAVS, but the mechanism of action remains unclear. Here we show that Riplet is required for RIG-I signaling in the presence of both short and long dsRNAs, establishing that Riplet activation does not depend upon RIG-I filament formation on long dsRNAs. Likewise, quantitative Riplet-RIG-I affinity measurements establish that Riplet interacts with RIG-I regardless of whether the receptor is bound to RNA. To understand this, we solved high-resolution cryo-EM structures of RIG-I/RNA/Riplet complexes, revealing molecular interfaces that control Riplet-mediated activation and enabling the formulation of a unified model for the role of Riplet in signaling.

The E3 ligase Riplet promotes RIG-I signaling independent of RIG-I oligomerization.,Wang W, Gotte B, Guo R, Pyle AM Nat Commun. 2023 Nov 11;14(1):7308. doi: 10.1038/s41467-023-42982-0. PMID:37951994<ref>PMID:37951994</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8g7v" style="background-color:#fffaf0;"></div>

==See Also==
*[[Ubiquitin protein ligase 3D structures|Ubiquitin protein ligase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Pyle AM]]
[[Category: Wang W]]