2vxt: Difference between revisions
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<StructureSection load='2vxt' size='340' side='right'caption='[[2vxt]], [[Resolution|resolution]] 1.49Å' scene=''> | <StructureSection load='2vxt' size='340' side='right'caption='[[2vxt]], [[Resolution|resolution]] 1.49Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[2vxt]] is a 3 chain structure with sequence from [ | <table><tr><td colspan='2'>[[2vxt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human] and [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2VXT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2VXT FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene></td></tr> | ||
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1j0s|1j0s]], [[2vxu|2vxu]], [[2vxv|2vxv]]</td></tr> | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1j0s|1j0s]], [[2vxu|2vxu]], [[2vxv|2vxv]]</div></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=2vxt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2vxt OCA], [https://pdbe.org/2vxt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2vxt RCSB], [https://www.ebi.ac.uk/pdbsum/2vxt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2vxt 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/> | ||
Revision as of 13:50, 7 July 2021
Crystal structure of human IL-18 complexed to murine reference antibody 125-2H FabCrystal structure of human IL-18 complexed to murine reference antibody 125-2H Fab
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 PubMedThe unique cytokine interleukin-18 (IL-18) acts synergistically with IL-12 to regulate T-helper 1 and 2 lymphocytes and, as such, seems to underlie the pathogenesis of various autoimmune and allergic diseases. Several anti-IL-18 agents are in clinical development, including the recombinant human antibody ABT-325, which is entering trials for autoimmune diseases. Given competing cytokine/receptor and cytokine/receptor decoy interactions, understanding the structural basis for recognition is critical for effective development of anti-cytokine therapies. Here we report three crystal structures: the murine antibody 125-2H Fab fragment bound to human IL-18, at 1.5 A resolution; the 125-2H Fab (2.3 A); and the ABT-325 Fab (1.5 A). These structures, along with human/mouse IL-18 chimera binding data, allow us to make three key observations relevant to the biology and antigenic recognition of IL-18 and related cytokines. First, several IL-18 residues shift dramatically (> 10 A) upon binding 125-2H, compared with unbound IL-18 (Kato, Z., Jee, J., Shikano, H., Mishima, M., Ohki, I., Ohnishi, H., Li, A., Hashimoto, K., Matsukuma, E., Omoya, K., Yamamoto, Y., Yoneda, T., Hara, T., Kondo, N., and Shirakawa, M. (2003) Nat. Struct. Biol. 10, 966-971). IL-18 thus exhibits plasticity that may be common to its interactions with other receptors. Related cytokines may exhibit similar plasticity. Second, ABT-325 and 125-2H differ significantly in combining site character and architecture, thus explaining their ability to bind IL-18 simultaneously at distinct epitopes. These data allow us to define the likely ABT-325 epitope and thereby explain the distinct neutralizing mechanisms of both antibodies. Third, given the high 125-2H potency, 10 well ordered water molecules are trapped upon complex formation in a cavity between two IL-18 loops and all six 125-2H complementarity-determining regions. Thus, counterintuitively, tight and specific antibody binding may in some cases be water-mediated. Unusual water-mediated antigenic recognition of the proinflammatory cytokine interleukin-18.,Argiriadi MA, Xiang T, Wu C, Ghayur T, Borhani DW J Biol Chem. 2009 Sep 4;284(36):24478-89. Epub 2009 Jun 24. PMID:19553661[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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