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| | ==Crystal Structure of Loop-Swapped Interleukin-36Ra== | | ==Crystal Structure of Loop-Swapped Interleukin-36Ra== |
| - | <StructureSection load='4p0j' size='340' side='right' caption='[[4p0j]], [[Resolution|resolution]] 2.30Å' scene=''> | + | <StructureSection load='4p0j' size='340' side='right'caption='[[4p0j]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4p0j]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4P0J OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4P0J FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4p0j]] 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=4P0J OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4P0J FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4p0k|4p0k]], [[4p0l|4p0l]]</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]] 2.298Å</td></tr> |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4p0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p0j OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4p0j RCSB], [http://www.ebi.ac.uk/pdbsum/4p0j PDBsum]</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=4p0j FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4p0j OCA], [https://pdbe.org/4p0j PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4p0j RCSB], [https://www.ebi.ac.uk/pdbsum/4p0j PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4p0j ProSAT]</span></td></tr> |
| - | <table> | + | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/I36RA_HUMAN I36RA_HUMAN]] Acrodermatitis continua suppurativa of Hallopeau;Generalized pustular psoriasis;Pustulosis palmaris et plantaris. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/I36RA_HUMAN I36RA_HUMAN] Acrodermatitis continua suppurativa of Hallopeau;Generalized pustular psoriasis;Pustulosis palmaris et plantaris. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/I36RA_HUMAN I36RA_HUMAN]] Is a highly and a specific antagonist of the IL-1 receptor-related protein 2/IL1RL2-mediated response to interleukin IL36G. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response. | + | [https://www.uniprot.org/uniprot/IL36G_HUMAN IL36G_HUMAN] Function as an agonist of NF-kappa B activation through the orphan IL-1-receptor-related protein 2/IL1RL2. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response.[https://www.uniprot.org/uniprot/I36RA_HUMAN I36RA_HUMAN] Is a highly and a specific antagonist of the IL-1 receptor-related protein 2/IL1RL2-mediated response to interleukin IL36G. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 4p0j" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Interleukin receptor antagonist|Interleukin receptor antagonist]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Guenther, S.]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Sundberg, E J.]] | + | [[Category: Large Structures]] |
| - | [[Category: Chimeric protein]] | + | [[Category: Guenther S]] |
| | + | [[Category: Sundberg EJ]] |
| Structural highlights
Disease
I36RA_HUMAN Acrodermatitis continua suppurativa of Hallopeau;Generalized pustular psoriasis;Pustulosis palmaris et plantaris. The disease is caused by mutations affecting the gene represented in this entry.
Function
IL36G_HUMAN Function as an agonist of NF-kappa B activation through the orphan IL-1-receptor-related protein 2/IL1RL2. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response.I36RA_HUMAN Is a highly and a specific antagonist of the IL-1 receptor-related protein 2/IL1RL2-mediated response to interleukin IL36G. Could constitute part of an independent signaling system analogous to interleukin-1 alpha (IL-1A), beta (IL-1B) receptor agonist and interleukin-1 receptor type I (IL-1R1), that is present in epithelial barriers and takes part in local inflammatory response.
Publication Abstract from PubMed
The IL-1 family consists of 11 cytokines that control a complex network of proinflammatory signals critical for regulating immune responses to infections. They also play a central role in numerous chronic inflammatory disorders. Accordingly, inhibiting the activities of these cytokines is an important therapeutic strategy for treating autoimmune diseases and lymphomas. Agonist cytokines in the IL-1 family activate signaling by binding their cognate receptor and then recruiting a receptor accessory protein. Conversely, antagonist cytokines bind their cognate receptor but prohibit recruitment of receptor accessory protein, which precludes functional signaling complexes. The IL-36 subfamily of cytokines is the most diverse, including three agonists and at least one antagonist, and is the least well-characterized group within this family. Signaling through the IL-36 receptor directly stimulates dendritic cells and primes naive CD4 T cells for Th1 responses. Appropriately balanced IL-36 signaling is a critical determinant of skin and lung health. IL-36 signaling has been presumed to function analogously to IL-1 signaling. In this study, we have defined molecular determinants of agonist and antagonist signaling through the IL-36 receptor. We present the crystal structure of IL-36gamma, which, to our knowledge, is the first reported structure of an IL-36 agonist. Using this structure as a guide, we designed a comprehensive series of IL-36 agonist/antagonist chimeric proteins for which we measured binding to the IL-36 receptor/IL-1 receptor accessory protein complex and functional activation and inhibition of signaling. Our data reveal how the fine specificity of IL-36 signaling is distinct from that of IL-1.
Molecular Determinants of Agonist and Antagonist Signaling through the IL-36 Receptor.,Gunther S, Sundberg EJ J Immunol. 2014 Jun 16. pii: 1400538. PMID:24935927[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gunther S, Sundberg EJ. Molecular Determinants of Agonist and Antagonist Signaling through the IL-36 Receptor. J Immunol. 2014 Jun 16. pii: 1400538. PMID:24935927 doi:http://dx.doi.org/10.4049/jimmunol.1400538
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