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6wcz
From Proteopedia
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==CryoEM structure of full-length ZIKV NS5-hSTAT2 complex== | ==CryoEM structure of full-length ZIKV NS5-hSTAT2 complex== | ||
| - | <StructureSection load='6wcz' size='340' side='right'caption='[[6wcz]]' scene=''> | + | <StructureSection load='6wcz' size='340' side='right'caption='[[6wcz]], [[Resolution|resolution]] 4.00Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WCZ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6wcz]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Zikv Zikv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WCZ OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6WCZ FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wcz OCA], [http://pdbe.org/6wcz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wcz RCSB], [http://www.ebi.ac.uk/pdbsum/6wcz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wcz ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">STAT2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GP1, A2G93_72125gpGP1, A2G93_72126gpGP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=64320 ZIKV])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6wcz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wcz OCA], [http://pdbe.org/6wcz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6wcz RCSB], [http://www.ebi.ac.uk/pdbsum/6wcz PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6wcz ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/STAT2_HUMAN STAT2_HUMAN]] Signal transducer and activator of transcription that mediates signaling by type I IFNs (IFN-alpha and IFN-beta). Following type I IFN binding to cell surface receptors, Jak kinases (TYK2 and JAK1) are activated, leading to tyrosine phosphorylation of STAT1 and STAT2. The phosphorylated STATs dimerize, associate with IRF9/ISGF3G to form a complex termed ISGF3 transcription factor, that enters the nucleus. ISGF3 binds to the IFN stimulated response element (ISRE) to activate the transcription of interferon stimulated genes, which drive the cell in an antiviral state.<ref>PMID:9020188</ref> [[http://www.uniprot.org/uniprot/A0A2R4LVT4_ZIKV A0A2R4LVT4_ZIKV]] Functions as a signal peptide for NS4B and is required for the interferon antagonism activity of the latter.[ARBA:ARBA00003504] Serine protease subunit NS2B: Required cofactor for the serine protease function of NS3.[PROSITE-ProRule:PRU00859] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Suppressing cellular signal transducers of transcription 2 (STAT2) is a common strategy that viruses use to establish infections, yet the detailed mechanism remains elusive, owing to a lack of structural information about the viral-cellular complex involved. Here, we report the cryo-EM and crystal structures of human STAT2 (hSTAT2) in complex with the non-structural protein 5 (NS5) of Zika virus (ZIKV) and dengue virus (DENV), revealing two-pronged interactions between NS5 and hSTAT2. First, the NS5 methyltransferase and RNA-dependent RNA polymerase (RdRP) domains form a conserved interdomain cleft harboring the coiled-coil domain of hSTAT2, thus preventing association of hSTAT2 with interferon regulatory factor 9. Second, the NS5 RdRP domain also binds the amino-terminal domain of hSTAT2. Disruption of these ZIKV NS5-hSTAT2 interactions compromised NS5-mediated hSTAT2 degradation and interferon suppression, and viral infection under interferon-competent conditions. Taken together, these results clarify the mechanism underlying the functional antagonism of STAT2 by both ZIKV and DENV. | ||
| + | |||
| + | Structural basis for STAT2 suppression by flavivirus NS5.,Wang B, Thurmond S, Zhou K, Sanchez-Aparicio MT, Fang J, Lu J, Gao L, Ren W, Cui Y, Veit EC, Hong H, Evans MJ, O'Leary SE, Garcia-Sastre A, Zhou ZH, Hai R, Song J Nat Struct Mol Biol. 2020 Aug 10. pii: 10.1038/s41594-020-0472-y. doi:, 10.1038/s41594-020-0472-y. PMID:32778820<ref>PMID:32778820</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wcz" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Adolfo | + | [[Category: Zikv]] |
| - | [[Category: Boxiao W]] | + | [[Category: Adolfo, G S]] |
| - | [[Category: Ethan | + | [[Category: Boxiao, W]] |
| - | [[Category: HeaJin H]] | + | [[Category: Ethan, C V]] |
| - | [[Category: Hong Z]] | + | [[Category: HeaJin, H]] |
| - | [[Category: Jian F]] | + | [[Category: Hong, Z]] |
| - | [[Category: Jikui S]] | + | [[Category: Jian, F]] |
| - | [[Category: Jiuwei L]] | + | [[Category: Jikui, S]] |
| - | [[Category: Kang Z]] | + | [[Category: Jiuwei, L]] |
| - | [[Category: Linfeng G]] | + | [[Category: Kang, Z]] |
| - | [[Category: Maria | + | [[Category: Linfeng, G]] |
| - | [[Category: Matthew | + | [[Category: Maria, T S]] |
| - | [[Category: Rong H]] | + | [[Category: Matthew, J E]] |
| - | [[Category: Sean | + | [[Category: Rong, H]] |
| - | [[Category: Stephanie T]] | + | [[Category: Sean, E O]] |
| - | [[Category: Wendan R]] | + | [[Category: Stephanie, T]] |
| - | [[Category: Yanxiang C]] | + | [[Category: Wendan, R]] |
| + | [[Category: Yanxiang, C]] | ||
| + | [[Category: Cryoem]] | ||
| + | [[Category: Hstat2]] | ||
| + | [[Category: Immune system]] | ||
| + | [[Category: Zikv ns5]] | ||
Revision as of 06:16, 14 October 2020
CryoEM structure of full-length ZIKV NS5-hSTAT2 complex
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Categories: Human | Large Structures | Zikv | Adolfo, G S | Boxiao, W | Ethan, C V | HeaJin, H | Hong, Z | Jian, F | Jikui, S | Jiuwei, L | Kang, Z | Linfeng, G | Maria, T S | Matthew, J E | Rong, H | Sean, E O | Stephanie, T | Wendan, R | Yanxiang, C | Cryoem | Hstat2 | Immune system | Zikv ns5
