1iar

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(New page: 200px<br /> <applet load="1iar" size="450" color="white" frame="true" align="right" spinBox="true" caption="1iar, resolution 2.3&Aring;" /> '''INTERLEUKIN-4 / RECE...)
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[[Image:1iar.gif|left|200px]]<br />
 
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<applet load="1iar" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1iar, resolution 2.3&Aring;" />
 
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'''INTERLEUKIN-4 / RECEPTOR ALPHA CHAIN COMPLEX'''<br />
 
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==Overview==
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==INTERLEUKIN-4 / RECEPTOR ALPHA CHAIN COMPLEX==
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Interleukin-4 (IL-4) is a principal regulatory cytokine during an immune, response and a crucial determinant for allergy and asthma. IL-4 binds with, high affinity and specificity to the ectodomain of the IL-4 receptor alpha, chain (IL4-BP). Subsequently, this intermediate complex recruits the, common gamma chain (gamma c), thereby initiating transmembrane signaling., The crystal structure of the intermediate complex between human IL-4 and, IL4-BP was determined at 2.3 A resolution. It reveals a novel spatial, orientation of the two proteins, a small but unexpected conformational, change in the receptor-bound IL-4, and an interface with three separate, clusters of trans-interacting residues. Novel insights on ligand binding, in the cytokine receptor family and a paradigm for receptors of IL-2, IL-7, IL-9, and IL-15, which all utilize gamma c, are provided.
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<StructureSection load='1iar' size='340' side='right'caption='[[1iar]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1iar]] is a 2 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=1IAR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1IAR 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]] 2.3&#8491;</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=1iar FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1iar OCA], [https://pdbe.org/1iar PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1iar RCSB], [https://www.ebi.ac.uk/pdbsum/1iar PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1iar ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[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>
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== Function ==
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[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.
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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/ia/1iar_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=1iar 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 (IL-4) is a principal regulatory cytokine during an immune response and a crucial determinant for allergy and asthma. IL-4 binds with high affinity and specificity to the ectodomain of the IL-4 receptor alpha chain (IL4-BP). Subsequently, this intermediate complex recruits the common gamma chain (gamma c), thereby initiating transmembrane signaling. The crystal structure of the intermediate complex between human IL-4 and IL4-BP was determined at 2.3 A resolution. It reveals a novel spatial orientation of the two proteins, a small but unexpected conformational change in the receptor-bound IL-4, and an interface with three separate clusters of trans-interacting residues. Novel insights on ligand binding in the cytokine receptor family and a paradigm for receptors of IL-2, IL-7, IL-9, and IL-15, which all utilize gamma c, are provided.
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==Disease==
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Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface.,Hage T, Sebald W, Reinemer P Cell. 1999 Apr 16;97(2):271-81. PMID:10219247<ref>PMID:10219247</ref>
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Known diseases associated with this structure: AIDS, slow progression to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147781 147781]], Atopy, susceptibility to OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=147781 147781]]
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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1IAR is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1IAR OCA].
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</div>
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<div class="pdbe-citations 1iar" style="background-color:#fffaf0;"></div>
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==Reference==
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==See Also==
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Crystal structure of the interleukin-4/receptor alpha chain complex reveals a mosaic binding interface., Hage T, Sebald W, Reinemer P, Cell. 1999 Apr 16;97(2):271-81. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=10219247 10219247]
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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: Protein complex]]
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[[Category: Large Structures]]
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[[Category: Hage, T.]]
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[[Category: Hage T]]
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[[Category: Reinemer, P.]]
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[[Category: Reinemer P]]
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[[Category: Sebald, W.]]
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[[Category: Sebald W]]
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[[Category: cytokine receptor]]
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[[Category: interleukin-4]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 17:28:12 2007''
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INTERLEUKIN-4 / RECEPTOR ALPHA CHAIN COMPLEX

PDB ID 1iar

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