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| | ==Crystal Structure of Human IL-18 in complex with Ectromelia virus IL-18 Binding Protein== | | ==Crystal Structure of Human IL-18 in complex with Ectromelia virus IL-18 Binding Protein== |
| - | <StructureSection load='3f62' size='340' side='right' caption='[[3f62]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3f62' size='340' side='right'caption='[[3f62]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3f62]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ectromelia_mousepox_virus Ectromelia mousepox virus] and [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F62 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3F62 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3f62]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ectromelia_mousepox_virus Ectromelia mousepox virus] and [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3F62 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3F62 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL18, IGIF, IL1F4 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL18, IGIF, IL1F4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3f62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f62 OCA], [http://pdbe.org/3f62 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3f62 RCSB], [http://www.ebi.ac.uk/pdbsum/3f62 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3f62 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=3f62 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3f62 OCA], [https://pdbe.org/3f62 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3f62 RCSB], [https://www.ebi.ac.uk/pdbsum/3f62 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3f62 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL18_HUMAN IL18_HUMAN]] Augments natural killer cell activity in spleen cells and stimulates interferon gamma production in T-helper type I cells. | + | [[https://www.uniprot.org/uniprot/IL18_HUMAN IL18_HUMAN]] Augments natural killer cell activity in spleen cells and stimulates interferon gamma production in T-helper type I cells. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Interleukin|Interleukin]] | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Ectromelia mousepox virus]] | | [[Category: Ectromelia mousepox virus]] |
| | [[Category: Human]] | | [[Category: Human]] |
| | + | [[Category: Large Structures]] |
| | [[Category: Deng, J]] | | [[Category: Deng, J]] |
| | [[Category: Krumm, B E]] | | [[Category: Krumm, B E]] |
| Structural highlights
Function
[IL18_HUMAN] Augments natural killer cell activity in spleen cells and stimulates interferon gamma production in T-helper type I cells.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Human interleukin-18 (hIL-18) is a cytokine that plays an important role in inflammation and host defense against microbes. Its activity is regulated in vivo by a naturally occurring antagonist, the human IL-18-binding protein (IL-18BP). Functional homologs of human IL-18BP are encoded by all orthopoxviruses, including variola virus, the causative agent of smallpox. They contribute to virulence by suppressing IL-18-mediated immune responses. Here, we describe the 2.0-A resolution crystal structure of an orthopoxvirus IL-18BP, ectromelia virus IL-18BP (ectvIL-18BP), in complex with hIL-18. The hIL-18 structure in the complex shows significant conformational change at the binding interface compared with the structure of ligand-free hIL-18, indicating that the binding is mediated by an induced-fit mechanism. EctvIL-18BP adopts a canonical Ig fold and interacts via one edge of its beta-sandwich with 3 cavities on the hIL-18 surface through extensive hydrophobic and hydrogen bonding interactions. Most of the ectvIL-18BP residues that participate in these interactions are conserved in both human and viral homologs, explaining their functional equivalence despite limited sequence homology. EctvIL-18BP blocks a putative receptor-binding site on IL-18, thus preventing IL-18 from engaging its receptor. Our structure provides insights into how IL-18BPs modulate hIL-18 activity. The revealed binding interface provides the basis for rational design of inhibitors against orthopoxvirus IL-18BP (for treating orthopoxvirus infection) or hIL-18 (for treating certain inflammatory and autoimmune diseases).
Structural basis for antagonism of human interleukin 18 by poxvirus interleukin 18-binding protein.,Krumm B, Meng X, Li Y, Xiang Y, Deng J Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20711-5. Epub 2008 Dec 22. PMID:19104048[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Krumm B, Meng X, Li Y, Xiang Y, Deng J. Structural basis for antagonism of human interleukin 18 by poxvirus interleukin 18-binding protein. Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20711-5. Epub 2008 Dec 22. PMID:19104048 doi:0809086106
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