3f62: Difference between revisions
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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 [ | <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 ([ | </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'>[ | <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 == | ||
[[ | [[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]] | ||
Revision as of 22:50, 20 October 2021
Crystal Structure of Human IL-18 in complex with Ectromelia virus IL-18 Binding ProteinCrystal Structure of Human IL-18 in complex with Ectromelia virus IL-18 Binding Protein
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 PubMedHuman 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 AlsoReferences
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