3bpo

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{{STRUCTURE_3bpo| PDB=3bpo | SCENE= }}
 
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===Crystal structure of the IL13-IL4R-IL13Ra ternary complex===
 
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{{ABSTRACT_PUBMED_18243101}}
 
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==Function==
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==Crystal structure of the IL13-IL4R-IL13Ra ternary complex==
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[[http://www.uniprot.org/uniprot/I13R1_HUMAN I13R1_HUMAN]] Binds with low affinity to interleukin-13 (IL13). Together with IL4RA can form a functional receptor for IL13. Also serves as an alternate accessory protein to the common cytokine receptor gamma chain for interleukin-4 (IL4) signaling, but cannot replace the function of IL2RG in allowing enhanced interleukin-2 (IL2) binding activity. [[http://www.uniprot.org/uniprot/IL4RA_HUMAN IL4RA_HUMAN]] Receptor for both interleukin 4 and interleukin 13. Couples to the JAK1/2/3-STAT6 pathway. The IL4 response is involved in promoting Th2 differentiation. The IL4/IL13 responses are involved in regulating IgE production and, chemokine and mucus production at sites of allergic inflammation. In certain cell types, can signal through activation of insulin receptor substrates, IRS1/IRS2.<ref>PMID:8124718</ref> Soluble IL4R (sIL4R) inhibits IL4-mediated cell proliferation and IL5 up-regulation by T-cells.<ref>PMID:8124718</ref>
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<StructureSection load='3bpo' size='340' side='right'caption='[[3bpo]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3bpo]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BPO FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3bpo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bpo OCA], [https://pdbe.org/3bpo PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bpo RCSB], [https://www.ebi.ac.uk/pdbsum/3bpo PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bpo ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN] Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:[https://omim.org/entry/607154 607154]. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure.
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== Function ==
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[https://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bp/3bpo_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3bpo ConSurf].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Interleukin-4 and Interleukin-13 are cytokines critical to the development of T cell-mediated humoral immune responses, which are associated with allergy and asthma, and exert their actions through three different combinations of shared receptors. Here we present the crystal structures of the complete set of type I (IL-4R alpha/gamma(c)/IL-4) and type II (IL-4R alpha/IL-13R alpha1/IL-4, IL-4R alpha/IL-13R alpha1/IL-13) ternary signaling complexes. The type I complex reveals a structural basis for gamma(c)'s ability to recognize six different gamma(c)-cytokines. The two type II complexes utilize an unusual top-mounted Ig-like domain on IL-13R alpha1 for a novel mode of cytokine engagement that contributes to a reversal in the IL-4 versus IL-13 ternary complex assembly sequences, which are mediated through substantially different recognition chemistries. We also show that the type II receptor heterodimer signals with different potencies in response to IL-4 versus IL-13 and suggest that the extracellular cytokine-receptor interactions are modulating intracellular membrane-proximal signaling events.
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==About this Structure==
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Molecular and structural basis of cytokine receptor pleiotropy in the interleukin-4/13 system.,LaPorte SL, Juo ZS, Vaclavikova J, Colf LA, Qi X, Heller NM, Keegan AD, Garcia KC Cell. 2008 Jan 25;132(2):259-72. PMID:18243101<ref>PMID:18243101</ref>
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[[3bpo]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPO OCA].
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==See Also==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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*[[Interleukin|Interleukin]]
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</div>
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*[[Interleukin receptor|Interleukin receptor]]
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<div class="pdbe-citations 3bpo" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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<ref group="xtra">PMID:018243101</ref><references group="xtra"/><references/>
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Garcia, K C.]]
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[[Category: Large Structures]]
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[[Category: Cytokine]]
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[[Category: Garcia KC]]
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[[Category: Cytokine-cytokine receptor complex]]
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[[Category: Glycoprotein]]
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[[Category: Il13]]
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[[Category: Il13r]]
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[[Category: Il4]]
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[[Category: Il4r]]
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[[Category: Immune response]]
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[[Category: Membrane]]
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[[Category: Phosphoprotein]]
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[[Category: Receptor]]
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[[Category: Secreted]]
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[[Category: Transmembrane]]
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Current revision

Crystal structure of the IL13-IL4R-IL13Ra ternary complex

PDB ID 3bpo

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