View source for 3bpn


==Crystal structure of the IL4-IL4R-IL13Ra ternary complex==
<StructureSection load='3bpn' size='340' side='right'caption='[[3bpn]], [[Resolution|resolution]] 3.02&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3bpn]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3BPN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3BPN FirstGlance]. <br>
</td></tr><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>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3bpl|3bpl]], [[3bpo|3bpo]]</div></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL4 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL4R, 582J2.1, IL4RA ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), IL13RA1, IL13R, IL13RA ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3bpn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3bpn OCA], [https://pdbe.org/3bpn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3bpn RCSB], [https://www.ebi.ac.uk/pdbsum/3bpn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3bpn ProSAT]</span></td></tr>
</table>
== Disease ==
[[https://www.uniprot.org/uniprot/IL4_HUMAN IL4_HUMAN]] Genetic variations in IL4 may be a cause of susceptibility to ischemic stroke (ISCHSTR) [MIM:[https://omim.org/entry/601367 601367]]; also known as cerebrovascular accident or cerebral infarction. A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors.<ref>PMID:14681304</ref>  
== Function ==
[[https://www.uniprot.org/uniprot/IL4_HUMAN IL4_HUMAN]] Participates in at least several B-cell activation processes as well as of other cell types. It is a costimulator of DNA-synthesis. It induces the expression of class II MHC molecules on resting B-cells. It enhances both secretion and cell surface expression of IgE and IgG1. It also regulates the expression of the low affinity Fc receptor for IgE (CD23) on both lymphocytes and monocytes. [[https://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. [[https://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>  
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/bp/3bpn_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</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=3bpn ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
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.

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>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3bpn" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Large Structures]]
[[Category: Garcia, K C]]
[[Category: B-cell activation]]
[[Category: Cytokine]]
[[Category: Cytokine-cytokine receptor complex]]
[[Category: Glycoprotein]]
[[Category: Growth factor]]
[[Category: Il13]]
[[Category: Il13r]]
[[Category: Il4]]
[[Category: Il4r]]
[[Category: Immune response]]
[[Category: Membrane]]
[[Category: Phosphoprotein]]
[[Category: Receptor]]
[[Category: Secreted]]
[[Category: Transmembrane]]