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2vxt

From Proteopedia

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Current revision

Crystal structure of human IL-18 complexed to murine reference antibody 125-2H Fab

Structural highlights

2vxt is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.49Å
Ligands:	,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

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

The 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.

References

↑ Argiriadi MA, Xiang T, Wu C, Ghayur T, Borhani DW. Unusual water-mediated antigenic recognition of the proinflammatory cytokine interleukin-18. J Biol Chem. 2009 Sep 4;284(36):24478-89. Epub 2009 Jun 24. PMID:19553661 doi:10.1074/jbc.M109.023887

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2vxt"

@@ Line 3: / Line 3: @@
 <StructureSection load='2vxt' size='340' side='right'caption='[[2vxt]], [[Resolution|resolution]] 1.49&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<table><tr><td colspan='2'>[[2vxt]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. 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" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.49&#8491;</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='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='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>
 == 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.
+[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 ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 36: / Line 36: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
-[[Category: Lk3 transgenic mice]]
+[[Category: Mus musculus]]
-[[Category: Argiriadi, M A]]
+[[Category: Argiriadi MA]]
-[[Category: Borhani, D W]]
+[[Category: Borhani DW]]
-[[Category: Ghayur, T]]
+[[Category: Ghayur T]]
-[[Category: Wu, C]]
+[[Category: Wu C]]
-[[Category: Xiang, T]]
+[[Category: Xiang T]]
-[[Category: Autoimmunity]]
-[[Category: Cytokine]]
-[[Category: Fab]]
-[[Category: Glycoprotein]]
-[[Category: Il-18]]
-[[Category: Immunoglobulin domain]]
-[[Category: Immunoglobulin v region]]
-[[Category: Secreted]]
-[[Category: Th1/th2 cell]]

2vxt

From Proteopedia

Current revision

Crystal structure of human IL-18 complexed to murine reference antibody 125-2H Fab

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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