7al7
From Proteopedia
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| - | ==== | + | ==The Crystal Structure of Human IL-18 in Complex With Human IL-18 Binding Protein== |
| - | <StructureSection load='7al7' size='340' side='right'caption='[[7al7]]' scene=''> | + | <StructureSection load='7al7' size='340' side='right'caption='[[7al7]], [[Resolution|resolution]] 1.80Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7al7]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Schistosoma_japonicum Schistosoma japonicum]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7AL7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7AL7 FirstGlance]. <br> |
| - | </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=7al7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7al7 OCA], [https://pdbe.org/7al7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7al7 RCSB], [https://www.ebi.ac.uk/pdbsum/7al7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7al7 ProSAT]</span></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]] 1.801Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CSO:S-HYDROXYCYSTEINE'>CSO</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</scene></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=7al7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7al7 OCA], [https://pdbe.org/7al7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7al7 RCSB], [https://www.ebi.ac.uk/pdbsum/7al7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7al7 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/I18BP_HUMAN I18BP_HUMAN] Disease susceptibility may be associated with variants affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/I18BP_HUMAN I18BP_HUMAN] Isoform A binds to IL-18 and inhibits its activity. Functions as an inhibitor of the early TH1 cytokine response.<ref>PMID:10023777</ref> <ref>PMID:10655506</ref> <ref>PMID:31213488</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Human Interleukin-18 (IL-18) is an omnipresent proinflammatory cytokine of the IL-1 family with central roles in autoimmune and inflammatory diseases and serves as a staple biomarker in the evaluation of inflammation in physiology and disease, including the inflammatory phase of COVID-19. The sequestration of IL-18 by its soluble decoy receptor IL-18-Binding Protein (IL-18BP) is critical to the regulation of IL-18 activity. Since an imbalance in expression and circulating levels of IL-18 is associated with disease, structural insights into how IL-18BP outcompetes binding of IL-18 by its cognate cell-surface receptors are highly desirable; however, the structure of human IL-18BP in complex with IL-18 has been elusive. Here, we elucidate the sequestration mechanism of human IL-18 mediated by IL-18BP based on the crystal structure of the IL-18:IL-18BP complex. These detailed structural snapshots reveal the interaction landscape leading to the ultra-high affinity of IL-18BP toward IL-18 and identify substantial differences with respect to previously characterized complexes of IL-18 with IL-18BP of viral origin. Furthermore, our structure captured a fortuitous higher-order assembly between IL-18 and IL-18BP coordinated by a disulfide-bond distal to the binding surface connecting IL-18 and IL-18BP molecules from different complexes, resulting in a novel tetramer with 2:2 stoichiometry. This tetrapartite assembly was found to restrain IL-18 activity more effectively than the canonical 1:1 complex. Collectively, our findings provide a framework for innovative, structure-driven therapeutic strategies and further functional interrogation of IL-18 in physiology and disease. | ||
| + | |||
| + | Structural basis of human IL-18 sequestration by the decoy receptor IL-18 binding protein in inflammation and tumor immunity.,Detry S, Andries J, Bloch Y, Gabay C, Clancy DM, Savvides SN J Biol Chem. 2022 May;298(5):101908. doi: 10.1016/j.jbc.2022.101908. Epub 2022 , Apr 6. PMID:35398099<ref>PMID:35398099</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7al7" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Schistosoma japonicum]] |
| + | [[Category: Andries J]] | ||
| + | [[Category: Bloch Y]] | ||
| + | [[Category: Clancy D]] | ||
| + | [[Category: Detry S]] | ||
| + | [[Category: Savvides SN]] | ||
Current revision
The Crystal Structure of Human IL-18 in Complex With Human IL-18 Binding Protein
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