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{{STRUCTURE_1p9m|  PDB=1p9m  |  SCENE=  }}
==Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex==
===Crystal structure of the hexameric human IL-6/IL-6 alpha receptor/gp130 complex===
<StructureSection load='1p9m' size='340' side='right' caption='[[1p9m]], [[Resolution|resolution]] 3.65&Aring;' scene=''>
{{ABSTRACT_PUBMED_12829785}}
== Structural highlights ==
 
<table><tr><td colspan='2'>[[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]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1P9M FirstGlance]. <br>
==Disease==
</td></tr><tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL6ST ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL6 OR IFNB2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]), IL6R ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens])</td></tr>
<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1p9m FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1p9m OCA], [http://www.rcsb.org/pdb/explore.do?structureId=1p9m RCSB], [http://www.ebi.ac.uk/pdbsum/1p9m PDBsum]</span></td></tr>
<table>
== Disease ==
[[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.  
[[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.  
== Function ==
[[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.
== 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/p9/1p9m_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/chain_selection.php?pdb_ID=2ata ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.


==Function==
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>
[[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.


==About this Structure==
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[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].
</div>


==See Also==
==See Also==
*[[Interleukin|Interleukin]]
*[[Interleukin|Interleukin]]
*[[Interleukin receptor|Interleukin receptor]]
*[[Interleukin receptor|Interleukin receptor]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:012829785</ref><ref group="xtra">PMID:015895091</ref><references group="xtra"/><references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Boulanger, M J.]]
[[Category: Boulanger, M J.]]

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