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| | ==Melanoma differentiation associated protein-5 Helicase domain complex with inhibitor Non-structural protein V== | | ==Melanoma differentiation associated protein-5 Helicase domain complex with inhibitor Non-structural protein V== |
| - | <StructureSection load='4i1s' size='340' side='right' caption='[[4i1s]], [[Resolution|resolution]] 2.29Å' scene=''> | + | <StructureSection load='4i1s' size='340' side='right'caption='[[4i1s]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i1s]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Pig Pig] and [http://en.wikipedia.org/wiki/Piv5 Piv5]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I1S OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I1S FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i1s]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Simian_virus_5_(strain_W3) Simian virus 5 (strain W3)] and [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4I1S OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I1S 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> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</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=4i1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i1s OCA], [https://pdbe.org/4i1s PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i1s RCSB], [https://www.ebi.ac.uk/pdbsum/4i1s PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i1s ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">MDA5 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9823 PIG]), P/V ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=11208 PIV5])</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=4i1s FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i1s OCA], [http://pdbe.org/4i1s PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i1s RCSB], [http://www.ebi.ac.uk/pdbsum/4i1s PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i1s ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/V_SV5 V_SV5]] Blocks host interferon signaling. Induces the ubiquitination and subsequent proteasome-mediated degradation of host STAT1. Acts as an adapter, linking host DDB1-Cullin 4 to STAT2/STAT1 complex. There is an absolute requirement of STAT2 in STAT1 degradation, as V binds specifically to STAT2. Might act as a chaperone keeping the viral nucleoprotein soluble. Interacts with host IFIH1/MDA5 to block its activity in the transduction pathway which leads to the activation of IFN-beta promoter, thus protecting the virus against cell antiviral state.<ref>PMID:15950997</ref> | + | [https://www.uniprot.org/uniprot/A7LCX1_PIG A7LCX1_PIG] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Pig]] | + | [[Category: Large Structures]] |
| - | [[Category: Piv5]] | + | [[Category: Sus scrofa]] |
| - | [[Category: Hopfner, K P]] | + | [[Category: Hopfner KP]] |
| - | [[Category: Motz, C]] | + | [[Category: Motz C]] |
| - | [[Category: Witte, G]] | + | [[Category: Witte G]] |
| - | [[Category: Helicase]]
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| - | [[Category: Hydrolase-hydrolase inhibitor complex]]
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| - | [[Category: Sf2-atpase]]
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| Structural highlights
Function
A7LCX1_PIG
Publication Abstract from PubMed
The RIG-I like receptor MDA5 senses cytoplasmic viral RNA and activates antiviral innate immunity. To reveal how paramyxoviruses counteract this response, we determined the crystal structure of the MDA5 ATP-hydrolysis domain in complex with the viral inhibitor V protein. The V protein unfolded the ATPase domain of MDA5 via a beta-hairpin motif and recognized a structural motif of MDA5 that is normally buried in the conserved helicase fold. This leads to disruption of the MDA5 ATP-hydrolysis site and prevention of RNA bound MDA5 filament formation. The structure explains why V proteins inactivate MDA5, but not RIG-I, and mutating only two amino acids in RIG-I induces robust V protein binding. Our results suggest an inhibition mechanism of RLR signalosome formation by unfolding of receptor and inhibitor.
Paramyxovirus V Proteins Disrupt the Fold of the RNA Sensor MDA5 to Inhibit Antiviral Signaling.,Motz C, Schuhmann KM, Kirchhofer A, Moldt M, Witte G, Conzelmann KK, Hopfner KP Science. 2013 Jan 17. PMID:23328395[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Motz C, Schuhmann KM, Kirchhofer A, Moldt M, Witte G, Conzelmann KK, Hopfner KP. Paramyxovirus V Proteins Disrupt the Fold of the RNA Sensor MDA5 to Inhibit Antiviral Signaling. Science. 2013 Jan 17. PMID:23328395 doi:http://dx.doi.org/10.1126/science.1230949
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