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| | <StructureSection load='5hn1' size='340' side='right'caption='[[5hn1]], [[Resolution|resolution]] 2.25Å' scene=''> | | <StructureSection load='5hn1' size='340' side='right'caption='[[5hn1]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hn1]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HN1 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hn1]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HN1 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.25Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL37, FIL1Z, IL1F7, IL1H4, IL1RP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5hn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn1 OCA], [http://pdbe.org/5hn1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hn1 RCSB], [http://www.ebi.ac.uk/pdbsum/5hn1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn1 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=5hn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hn1 OCA], [https://pdbe.org/5hn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hn1 RCSB], [https://www.ebi.ac.uk/pdbsum/5hn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hn1 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL37_HUMAN IL37_HUMAN]] Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.<ref>PMID:18390730</ref> <ref>PMID:20935647</ref> | + | [https://www.uniprot.org/uniprot/IL37_HUMAN IL37_HUMAN] Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.<ref>PMID:18390730</ref> <ref>PMID:20935647</ref> |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Ellisdon, A M]] | + | [[Category: Ellisdon AM]] |
| - | [[Category: Nold, M F]] | + | [[Category: Nold MF]] |
| - | [[Category: Nold-Petry, C A]] | + | [[Category: Nold-Petry CA]] |
| - | [[Category: Whisstock, J C]] | + | [[Category: Whisstock JC]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Interleukin-1 cytokine inflammation interleukin-18]]
| + | |
| Structural highlights
Function
IL37_HUMAN Suppressor of innate inflammatory and immune responses involved in curbing excessive inflammation. This function requires SMAD3. Suppresses, or reduces, proinflammatory cytokine production, including IL1A and IL6, as well as CCL12, CSF1, CSF2, CXCL13, IL1B, IL23A and IL1RN, but spares anti-inflammatory cytokines. Inhibits dendritic cell activation.[1] [2]
Publication Abstract from PubMed
Dysregulation of the inflammatory response underlies numerous diseases. Although most interleukin-1 family cytokines are proinflammatory, human interleukin-37 (IL-37) is a powerful, broad-spectrum inhibitor of inflammation and immunity. We determined the crystal structure of IL-37 to establish the anti-inflammatory mechanism of this key cytokine in view of developing IL-37-based therapies. We found that two beta-trefoil fold IL-37 molecules form a head-to-head dimer that is stable in solution. IL-37 variants mutated to convert the cytokine into an obligate monomer were up to 13-fold more effective than the dimer in suppressing proinflammatory events both in primary human blood cells and in vivo in murine endotoxic shock. Therapeutic exploitation of the powerful anti-inflammatory properties of monomeric IL-37 may prove beneficial in treating a wide range of inflammatory and autoimmune disorders.
Homodimerization attenuates the anti-inflammatory activity of interleukin-37.,Ellisdon AM, Nold-Petry CA, D'Andrea L, Cho SX, Lao JC, Rudloff I, Ngo D, Lo CY, Soares da Costa TP, Perugini MA, Conroy PJ, Whisstock JC, Nold MF Sci Immunol. 2017 Feb 10;2(8). pii: eaaj1548. doi: 10.1126/sciimmunol.aaj1548. PMID:28783685[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sharma S, Kulk N, Nold MF, Graf R, Kim SH, Reinhardt D, Dinarello CA, Bufler P. The IL-1 family member 7b translocates to the nucleus and down-regulates proinflammatory cytokines. J Immunol. 2008 Apr 15;180(8):5477-82. PMID:18390730
- ↑ Nold MF, Nold-Petry CA, Zepp JA, Palmer BE, Bufler P, Dinarello CA. IL-37 is a fundamental inhibitor of innate immunity. Nat Immunol. 2010 Nov;11(11):1014-22. doi: 10.1038/ni.1944. Epub 2010 Oct 10. PMID:20935647 doi:http://dx.doi.org/10.1038/ni.1944
- ↑ Ellisdon AM, Nold-Petry CA, D'Andrea L, Cho SX, Lao JC, Rudloff I, Ngo D, Lo CY, Soares da Costa TP, Perugini MA, Conroy PJ, Whisstock JC, Nold MF. Homodimerization attenuates the anti-inflammatory activity of interleukin-37. Sci Immunol. 2017 Feb 10;2(8). pii: eaaj1548. doi: 10.1126/sciimmunol.aaj1548. PMID:28783685 doi:http://dx.doi.org/10.1126/sciimmunol.aaj1548
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