1p9m

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{{STRUCTURE_1p9m| PDB=1p9m | SCENE= }}
 
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===Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex===
 
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{{ABSTRACT_PUBMED_12829785}}
 
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==Disease==
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==Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex==
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[[http://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN]] Genetic variations in IL6 are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[http://omim.org/entry/604302 604302]]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men.
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<StructureSection load='1p9m' size='340' side='right'caption='[[1p9m]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1p9m]] 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=1P9M OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1P9M 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]] 3.65&#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=1p9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9m OCA], [https://pdbe.org/1p9m PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1p9m RCSB], [https://www.ebi.ac.uk/pdbsum/1p9m PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1p9m ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/IL6RB_HUMAN IL6RB_HUMAN] Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development (By similarity). The type I OSM receptor is capable of transducing OSM-specific signaling events.
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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/p9/1p9m_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=1p9m 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-6 (IL-6) is an immunoregulatory cytokine that activates a cell-surface signaling assembly composed of IL-6, the IL-6 alpha-receptor (IL-6Ralpha), and the shared signaling receptor gp130. The 3.65 angstrom-resolution structure of the extracellular signaling complex reveals a hexameric, interlocking assembly mediated by a total of 10 symmetry-related, thermodynamically coupled interfaces. Assembly of the hexameric complex occurs sequentially: IL-6 is first engaged by IL-6Ralpha and then presented to gp130in the proper geometry to facilitate a cooperative transition into the high-affinity, signaling-competent hexamer. The quaternary structures of other IL-6/IL-12 family signaling complexes are likely constructed by means of a similar topological blueprint.
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==Function==
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Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex.,Boulanger MJ, Chow DC, Brevnova EE, Garcia KC Science. 2003 Jun 27;300(5628):2101-4. PMID:12829785<ref>PMID:12829785</ref>
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[[http://www.uniprot.org/uniprot/IL6RB_HUMAN IL6RB_HUMAN]] Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development (By similarity). The type I OSM receptor is capable of transducing OSM-specific signaling events. [[http://www.uniprot.org/uniprot/IL6RA_HUMAN IL6RA_HUMAN]] Part of the receptor for interleukin 6. Binds to IL6 with low affinity, but does not transduce a signal. Signal activation necessitate an association with IL6ST. Activation may lead to the regulation of the immune response, acute-phase reactions and hematopoiesis.<ref>PMID:11017875</ref><ref>PMID:16270750</ref> Low concentration of a soluble form of IL6 receptor acts as an agonist of IL6 activity.<ref>PMID:11017875</ref><ref>PMID:16270750</ref> [[http://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN]] Cytokine with a wide variety of biological functions. It is a potent inducer of the acute phase response. Plays an essential role in the final differentiation of B-cells into Ig-secreting cells Involved in lymphocyte and monocyte differentiation. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Also acts as a myokine. It is discharged into the bloodstream after muscle contraction and acts to increase the breakdown of fats and to improve insulin resistance.
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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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[[1p9m]] 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=1P9M OCA].
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</div>
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<div class="pdbe-citations 1p9m" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Interleukin|Interleukin]]
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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*[[Interleukin receptor|Interleukin receptor]]
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*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:012829785</ref><ref group="xtra">PMID:015895091</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Boulanger, M J.]]
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[[Category: Large Structures]]
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[[Category: Brevnova, E E.]]
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[[Category: Boulanger MJ]]
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[[Category: Chow, D C.]]
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[[Category: Brevnova EE]]
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[[Category: Garcia, K C.]]
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[[Category: Chow DC]]
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[[Category: Cytokine]]
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[[Category: Garcia KC]]
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[[Category: Four helix bundle]]
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[[Category: Gp130]]
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[[Category: Ig domain]]
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[[Category: Interleukin-6]]
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[[Category: Signaling protein-cytokine complex]]
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Current revision

Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex

PDB ID 1p9m

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