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| | == Structural highlights == | | == Structural highlights == |
| | <table><tr><td colspan='2'>[[3cm3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CM3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CM3 FirstGlance]. <br> | | <table><tr><td colspan='2'>[[3cm3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Vaccinia_virus Vaccinia virus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CM3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CM3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.32Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2rf6|2rf6]], [[3ceo|3ceo]]</div></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BME:BETA-MERCAPTOETHANOL'>BME</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">H1 ORF ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10245 Vaccinia virus])</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=3cm3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cm3 OCA], [https://pdbe.org/3cm3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cm3 RCSB], [https://www.ebi.ac.uk/pdbsum/3cm3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cm3 ProSAT]</span></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=3cm3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cm3 OCA], [https://pdbe.org/3cm3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cm3 RCSB], [https://www.ebi.ac.uk/pdbsum/3cm3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cm3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/DUSP_VACCW DUSP_VACCW]] Serine/Tyrosine phosphatase which down-regulates cellular antiviral response by dephosphorylating activated host STAT1 and blocking interferon (IFN)-stimulated innate immune responses. Dephosphorylates the A17 protein.<ref>PMID:10438817</ref> <ref>PMID:11238845</ref> <ref>PMID:1848923</ref> <ref>PMID:18593332</ref> <ref>PMID:21362620</ref>
| + | [https://www.uniprot.org/uniprot/DUSP_VACCW DUSP_VACCW] Serine/Tyrosine phosphatase which down-regulates cellular antiviral response by dephosphorylating activated host STAT1 and blocking interferon (IFN)-stimulated innate immune responses. Dephosphorylates the A17 protein.<ref>PMID:10438817</ref> <ref>PMID:11238845</ref> <ref>PMID:1848923</ref> <ref>PMID:18593332</ref> <ref>PMID:21362620</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Vaccinia virus]] | | [[Category: Vaccinia virus]] |
| - | [[Category: Cingolani, G]] | + | [[Category: Cingolani G]] |
| - | [[Category: Koksal, A C]] | + | [[Category: Koksal AC]] |
| - | [[Category: Dual-specificity phosphatase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Late protein]]
| + | |
| - | [[Category: Protein phosphatase]]
| + | |
| - | [[Category: Vh1]]
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| Structural highlights
Function
DUSP_VACCW Serine/Tyrosine phosphatase which down-regulates cellular antiviral response by dephosphorylating activated host STAT1 and blocking interferon (IFN)-stimulated innate immune responses. Dephosphorylates the A17 protein.[1] [2] [3] [4] [5]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
The Vaccinia virus H1 gene product, VH1, is a dual specificity phosphatase that down-regulates the cellular antiviral response by dephosphorylating STAT1. The crystal structure of VH1, determined at 1.32 A resolution, reveals a novel dimeric quaternary structure, which exposes two active sites spaced approximately 39 A away from each other. VH1 forms a stable dimer via an extensive domain swap of the N-terminal helix (residues 1-20). In vitro, VH1 can dephosphorylate activated STAT1, in a reaction that is competed by the nuclear transport adapter importin alpha5. Interestingly, VH1 is inactive with respect to STAT1 bound to DNA, suggesting that the viral phosphatase acts predominantly on the cytoplasmic pool of activated STAT1. We propose that the dimeric quaternary structure of VH1 is essential for specific recognition of activated STAT1, which prevents its nuclear translocation, thus blocking interferon-gamma signal transduction and antiviral response.
Dimeric quaternary structure of the prototypical dual specificity phosphatase VH1.,Koksal AC, Nardozzi JD, Cingolani G J Biol Chem. 2009 Apr 10;284(15):10129-37. Epub 2009 Feb 10. PMID:19211553[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Derrien M, Punjabi A, Khanna M, Grubisha O, Traktman P. Tyrosine phosphorylation of A17 during vaccinia virus infection: involvement of the H1 phosphatase and the F10 kinase. J Virol. 1999 Sep;73(9):7287-96. PMID:10438817
- ↑ Najarro P, Traktman P, Lewis JA. Vaccinia virus blocks gamma interferon signal transduction: viral VH1 phosphatase reverses Stat1 activation. J Virol. 2001 Apr;75(7):3185-96. PMID:11238845 doi:http://dx.doi.org/10.1128/JVI.75.7.3185-3196.2001
- ↑ Guan KL, Broyles SS, Dixon JE. A Tyr/Ser protein phosphatase encoded by vaccinia virus. Nature. 1991 Mar 28;350(6316):359-62. PMID:1848923 doi:http://dx.doi.org/10.1038/350359a0
- ↑ Mann BA, Huang JH, Li P, Chang HC, Slee RB, O'Sullivan A, Anita M, Yeh N, Klemsz MJ, Brutkiewicz RR, Blum JS, Kaplan MH. Vaccinia virus blocks Stat1-dependent and Stat1-independent gene expression induced by type I and type II interferons. J Interferon Cytokine Res. 2008 Jun;28(6):367-80. doi: 10.1089/jir.2007.0113. PMID:18593332 doi:http://dx.doi.org/10.1089/jir.2007.0113
- ↑ Koksal AC, Cingolani G. Dimerization of Vaccinia virus VH1 is essential for dephosphorylation of STAT1 at tyrosine 701. J Biol Chem. 2011 Apr 22;286(16):14373-82. doi: 10.1074/jbc.M111.226357. Epub, 2011 Mar 1. PMID:21362620 doi:http://dx.doi.org/10.1074/jbc.M111.226357
- ↑ Koksal AC, Nardozzi JD, Cingolani G. Dimeric quaternary structure of the prototypical dual specificity phosphatase VH1. J Biol Chem. 2009 Apr 10;284(15):10129-37. Epub 2009 Feb 10. PMID:19211553 doi:10.1074/jbc.M808362200
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