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| | <StructureSection load='6u6u' size='340' side='right'caption='[[6u6u]], [[Resolution|resolution]] 2.31Å' scene=''> | | <StructureSection load='6u6u' size='340' side='right'caption='[[6u6u]], [[Resolution|resolution]] 2.31Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6u6u]] is a 3 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=6U6U OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6U6U FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6u6u]] is a 3 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=6U6U OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6U6U FirstGlance]. <br> |
| - | </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>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.31Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL1RL2, IL1RRP2 ([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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=6u6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u6u OCA], [http://pdbe.org/6u6u PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6u6u RCSB], [http://www.ebi.ac.uk/pdbsum/6u6u PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6u6u 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=6u6u FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6u6u OCA], [https://pdbe.org/6u6u PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6u6u RCSB], [https://www.ebi.ac.uk/pdbsum/6u6u PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6u6u ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/ILRL2_HUMAN ILRL2_HUMAN]] Receptor for interleukin-36 (IL36A, IL36B and IL36G). After binding to interleukin-36 associates with the coreceptor IL1RAP to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways (By similarity). The IL-36 signaling system is thought to be present in epithelial barriers and to take part in local inflammatory response; it is similar to the IL-1 system. Seems to be involved in skin inflammatory response by induction of the IL-23/IL-17/IL-22 pathway.[UniProtKB:Q9ERS7]<ref>PMID:11466363</ref> | + | [https://www.uniprot.org/uniprot/ILRL2_HUMAN ILRL2_HUMAN] Receptor for interleukin-36 (IL36A, IL36B and IL36G). After binding to interleukin-36 associates with the coreceptor IL1RAP to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways (By similarity). The IL-36 signaling system is thought to be present in epithelial barriers and to take part in local inflammatory response; it is similar to the IL-1 system. Seems to be involved in skin inflammatory response by induction of the IL-23/IL-17/IL-22 pathway.[UniProtKB:Q9ERS7]<ref>PMID:11466363</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 6u6u" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 6u6u" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Antibody 3D structures|Antibody 3D structures]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Farrow, N A]] | + | [[Category: Farrow NA]] |
| - | [[Category: Larson, E T]] | + | [[Category: Larson ET]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Il36r]]
| + | |
| Structural highlights
Function
ILRL2_HUMAN Receptor for interleukin-36 (IL36A, IL36B and IL36G). After binding to interleukin-36 associates with the coreceptor IL1RAP to form the interleukin-36 receptor complex which mediates interleukin-36-dependent activation of NF-kappa-B, MAPK and other pathways (By similarity). The IL-36 signaling system is thought to be present in epithelial barriers and to take part in local inflammatory response; it is similar to the IL-1 system. Seems to be involved in skin inflammatory response by induction of the IL-23/IL-17/IL-22 pathway.[UniProtKB:Q9ERS7][1]
Publication Abstract from PubMed
Cellular signaling via binding of the cytokines IL-36alpha, beta and gamma along with binding of the accessory protein IL-36RAcP, to their cognate receptor IL-36R is believed to play a major role in epithelial and immune cell mediated inflammation responses. Antagonizing the signaling cascade that results from these binding events via a directed monoclonal antibody provides an opportunity to suppress such immune responses. We report here the molecular structure of a complex between an extra-cellular portion of human IL-36R and a Fab derived from a high affinity anti-IL-36R neutralizing monoclonal antibody at 2.3a resolution. This structure, the first of IL-36R, reveals similarities with other structurally characterized IL-1R family members and elucidates the molecular determinants leading to the high affinity binding of the monoclonal antibody. The structure of the complex reveals that the epitope recognized by the Fab is remote from both the putative ligand and accessory protein binding interfaces on IL-36R, suggesting that the functional activity of the antibody is non-competitive for these binding events. This article is protected by copyright. All rights reserved.
X-ray Crystal Structure Localizes the Mechanism of Inhibition of an IL-36R Antagonist Monoclonal Antibody to Interaction with Ig1 and Ig2 ECDs.,Larson ET, Brennan DL, Hickey ER, Ganesan R, Kroe-Barrett R, Farrow NA Protein Sci. 2020 Apr 2. doi: 10.1002/pro.3862. PMID:32239732[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Debets R, Timans JC, Homey B, Zurawski S, Sana TR, Lo S, Wagner J, Edwards G, Clifford T, Menon S, Bazan JF, Kastelein RA. Two novel IL-1 family members, IL-1 delta and IL-1 epsilon, function as an antagonist and agonist of NF-kappa B activation through the orphan IL-1 receptor-related protein 2. J Immunol. 2001 Aug 1;167(3):1440-6. doi: 10.4049/jimmunol.167.3.1440. PMID:11466363 doi:http://dx.doi.org/10.4049/jimmunol.167.3.1440
- ↑ Larson ET, Brennan DL, Hickey ER, Ganesan R, Kroe-Barrett R, Farrow NA. X-ray Crystal Structure Localizes the Mechanism of Inhibition of an IL-36R Antagonist Monoclonal Antibody to Interaction with Ig1 and Ig2 ECDs. Protein Sci. 2020 Apr 2. doi: 10.1002/pro.3862. PMID:32239732 doi:http://dx.doi.org/10.1002/pro.3862
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