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| | ==Crystal structure of p202 HIN1 in complex with 20-mer dsDNA== | | ==Crystal structure of p202 HIN1 in complex with 20-mer dsDNA== |
| - | <StructureSection load='4l5r' size='340' side='right' caption='[[4l5r]], [[Resolution|resolution]] 1.87Å' scene=''> | + | <StructureSection load='4l5r' size='340' side='right'caption='[[4l5r]], [[Resolution|resolution]] 1.87Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4l5r]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L5R OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4L5R FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4l5r]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4L5R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4L5R FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</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]] 1.873Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ifi202, Ifi202a, Ifi202b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene></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=4l5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l5r OCA], [http://pdbe.org/4l5r PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4l5r RCSB], [http://www.ebi.ac.uk/pdbsum/4l5r PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4l5r 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=4l5r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4l5r OCA], [https://pdbe.org/4l5r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4l5r RCSB], [https://www.ebi.ac.uk/pdbsum/4l5r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4l5r ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IFI2_MOUSE IFI2_MOUSE]] Inhibits the transcriptional activity of several transcription factors, including NF-kappa-B p50 and p65, FOS, JUN, E2F1, E2F4, MYOD1 and myogenin. Has anti-apoptotic effects due to inhibition of the transcriptional activity of p53. Binds dsDNA in the cytosol. Is involved in innate immune response and has anti-inflammatory activity. Inhibits caspase activation in response to cytosolic DNA and may inhibit the activation of the AIM2 inflammasome, probably via association with AIM2.<ref>PMID:16670293</ref> <ref>PMID:19131592</ref> | + | [https://www.uniprot.org/uniprot/IFI2_MOUSE IFI2_MOUSE] Inhibits the transcriptional activity of several transcription factors, including NF-kappa-B p50 and p65, FOS, JUN, E2F1, E2F4, MYOD1 and myogenin. Has anti-apoptotic effects due to inhibition of the transcriptional activity of p53. Binds dsDNA in the cytosol. Is involved in innate immune response and has anti-inflammatory activity. Inhibits caspase activation in response to cytosolic DNA and may inhibit the activation of the AIM2 inflammasome, probably via association with AIM2.<ref>PMID:16670293</ref> <ref>PMID:19131592</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Mouse p202 containing two hemopoietic expression, interferon inducibility, nuclear localization (HIN) domains antagonizes AIM2 inflammasome signaling and potentially modifies lupus susceptibility. We found that only HIN1 of p202 binds double-stranded DNA (dsDNA), while HIN2 forms a homotetramer. Crystal structures of HIN1 revealed that dsDNA is bound on face opposite the site used in AIM2 and IFI16. The structure of HIN2 revealed a dimer of dimers, the face analogous to the HIN1 dsDNA binding site being a dimerization interface. Electron microscopy imaging showed that HIN1 is flexibly linked to HIN2 in p202, and tetramerization provided enhanced avidity for dsDNA. Surprisingly, HIN2 of p202 interacts with the AIM HIN domain. We propose that this results in a spatial separation of the AIM2 pyrin domains, and indeed p202 prevented the dsDNA-dependent clustering of apoptosis-associated speck-like protein containing caspase recruitment domain (ASC) and AIM2 inflammasome activation. We hypothesize that while p202 was evolutionarily selected to limit AIM2-mediated inflammation in some mouse strains, the same mechanism contributes to increased interferon production and lupus susceptibility.
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| - | | + | |
| - | Molecular Mechanism for p202-Mediated Specific Inhibition of AIM2 Inflammasome Activation.,Yin Q, Sester DP, Tian Y, Hsiao YS, Lu A, Cridland JA, Sagulenko V, Thygesen SJ, Choubey D, Hornung V, Walz T, Stacey KJ, Wu H Cell Rep. 2013 Jul 25;4(2):327-39. doi: 10.1016/j.celrep.2013.06.024. Epub 2013, Jul 11. PMID:23850291<ref>PMID:23850291</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
| + | |
| - | <div class="pdbe-citations 4l5r" style="background-color:#fffaf0;"></div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Tian, Y]] | + | [[Category: Mus musculus]] |
| - | [[Category: Wu, H]] | + | [[Category: Tian Y]] |
| - | [[Category: Yin, Q]] | + | [[Category: Wu H]] |
| - | [[Category: Dna binding protein-dna complex]] | + | [[Category: Yin Q]] |
| - | [[Category: Dsdna binding domain]]
| + | |
| - | [[Category: Hin200]]
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| - | [[Category: Ob fold]]
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| Structural highlights
Function
IFI2_MOUSE Inhibits the transcriptional activity of several transcription factors, including NF-kappa-B p50 and p65, FOS, JUN, E2F1, E2F4, MYOD1 and myogenin. Has anti-apoptotic effects due to inhibition of the transcriptional activity of p53. Binds dsDNA in the cytosol. Is involved in innate immune response and has anti-inflammatory activity. Inhibits caspase activation in response to cytosolic DNA and may inhibit the activation of the AIM2 inflammasome, probably via association with AIM2.[1] [2]
References
- ↑ Xin H, D'Souza S, Jorgensen TN, Vaughan AT, Lengyel P, Kotzin BL, Choubey D. Increased expression of Ifi202, an IFN-activatable gene, in B6.Nba2 lupus susceptible mice inhibits p53-mediated apoptosis. J Immunol. 2006 May 15;176(10):5863-70. PMID:16670293
- ↑ Roberts TL, Idris A, Dunn JA, Kelly GM, Burnton CM, Hodgson S, Hardy LL, Garceau V, Sweet MJ, Ross IL, Hume DA, Stacey KJ. HIN-200 proteins regulate caspase activation in response to foreign cytoplasmic DNA. Science. 2009 Feb 20;323(5917):1057-60. doi: 10.1126/science.1169841. Epub 2009, Jan 8. PMID:19131592 doi:10.1126/science.1169841
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