View source for 6gkh


==CryoEM structure of the MDA5-dsRNA filament in complex with ADP-AlF4==
<SX load='6gkh' size='340' side='right' viewer='molstar' caption='[[6gkh]], [[Resolution|resolution]] 4.06&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6gkh]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Pseudomonas_virus_phi6 Pseudomonas virus phi6]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GKH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GKH 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]] 4.06&#8491;</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=ALF:TETRAFLUOROALUMINATE+ION'>ALF</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=6gkh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gkh OCA], [https://pdbe.org/6gkh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gkh RCSB], [https://www.ebi.ac.uk/pdbsum/6gkh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gkh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/IFIH1_MOUSE IFIH1_MOUSE] 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 mRNA lacking 2'-O-methylation at their 5' cap and long-dsRNA (>1 kb in length). 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. Responsible for detecting the Picornaviridae family members such as encephalomyocarditis virus (EMCV), mengo encephalomyocarditis virus (ENMG), and theiler's murine encephalomyelitis virus (TMEV). Can also detect other viruses such as dengue virus (DENV), west Nile virus (WNV), and reovirus. Also involved in antiviral signaling in response to viruses containing a dsDNA genome, such as vaccinia virus. Plays an important role in amplifying innate immune signaling through recognition of RNA metabolites that are produced during virus infection by ribonuclease L (RNase L). May play an important role in enhancing natural killer cell function and may be involved in growth inhibition and apoptosis in several tumor cell lines.<ref>PMID:12015121</ref> <ref>PMID:16625202</ref> <ref>PMID:17942531</ref> <ref>PMID:19656871</ref> <ref>PMID:21217758</ref> 
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== Publication Abstract from PubMed ==
Double-stranded RNA (dsRNA) is a potent proinflammatory signature of viral infection. Long cytosolic dsRNA is recognized by MDA5. The cooperative assembly of MDA5 into helical filaments on dsRNA nucleates the assembly of a multiprotein type I interferon signaling platform. Here, we determined cryoelectron microscopy (cryo-EM) structures of MDA5-dsRNA filaments with different helical twists and bound nucleotide analogs at resolutions sufficient to build and refine atomic models. The structures identify the filament-forming interfaces, which encode the dsRNA binding cooperativity and length specificity of MDA5. The predominantly hydrophobic interface contacts confer flexibility, reflected in the variable helical twist within filaments. Mutation of filament-forming residues can result in loss or gain of signaling activity. Each MDA5 molecule spans 14 or 15 RNA base pairs, depending on the twist. Variations in twist also correlate with variations in the occupancy and type of nucleotide in the active site, providing insights on how ATP hydrolysis contributes to MDA5-dsRNA recognition.

Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis.,Yu Q, Qu K, Modis Y Mol Cell. 2018 Nov 7. pii: S1097-2765(18)30844-X. doi:, 10.1016/j.molcel.2018.10.012. PMID:30449722<ref>PMID:30449722</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 6gkh" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</SX>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Pseudomonas virus phi6]]
[[Category: Modis Y]]
[[Category: Qu K]]
[[Category: Yu Q]]