5e3h
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Structural Basis for RNA Recognition and Activation of RIG-I== | |
| + | <StructureSection load='5e3h' size='340' side='right'caption='[[5e3h]], [[Resolution|resolution]] 2.70Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5e3h]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3tmi 3tmi]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E3H OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E3H FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.7Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=BEF:BERYLLIUM+TRIFLUORIDE+ION'>BEF</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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=5e3h FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e3h OCA], [https://pdbe.org/5e3h PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e3h RCSB], [https://www.ebi.ac.uk/pdbsum/5e3h PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e3h 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: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.<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:28469175</ref> <ref>PMID:29117565</ref> <ref>PMID:31006531</ref> <ref>PMID:34935440</ref> <ref>PMID:17974005</ref> <ref>PMID:21616437</ref> <ref>PMID:21884169</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer. The helicase and repressor domains (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM. | ||
| - | + | Structural basis of RNA recognition and activation by innate immune receptor RIG-I.,Jiang F, Ramanathan A, Miller MT, Tang GQ, Gale M, Patel SS, Marcotrigiano J Nature. 2011 Sep 25. doi: 10.1038/nature10537. PMID:21947008<ref>PMID:21947008</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5e3h" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Marcotrigiano | + | ==See Also== |
| + | *[[Helicase 3D structures|Helicase 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Synthetic construct]] | ||
| + | [[Category: Jiang F]] | ||
| + | [[Category: Marcotrigiano J]] | ||
| + | [[Category: Miller MT]] | ||
Current revision
Structural Basis for RNA Recognition and Activation of RIG-I
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