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| | ==Solution structure of mouse IL-6== | | ==Solution structure of mouse IL-6== |
| - | <StructureSection load='2l3y' size='340' side='right'caption='[[2l3y]], [[NMR_Ensembles_of_Models | 52 NMR models]]' scene=''> | + | <StructureSection load='2l3y' size='340' side='right'caption='[[2l3y]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l3y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L3Y FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l3y]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L3Y OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L3Y FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Il6, Il-6 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | </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=2l3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l3y OCA], [https://pdbe.org/2l3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l3y RCSB], [https://www.ebi.ac.uk/pdbsum/2l3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l3y ProSAT]</span></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=2l3y FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l3y OCA], [https://pdbe.org/2l3y PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l3y RCSB], [https://www.ebi.ac.uk/pdbsum/2l3y PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l3y ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/IL6_MOUSE IL6_MOUSE]] 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. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. 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. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.<ref>PMID:16990136</ref>
| + | [https://www.uniprot.org/uniprot/IL6_MOUSE IL6_MOUSE] 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. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. 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. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.<ref>PMID:16990136</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Carr, M D]] | + | [[Category: Carr MD]] |
| - | [[Category: Carrington, B]] | + | [[Category: Carrington B]] |
| - | [[Category: Henry, A J]] | + | [[Category: Henry AJ]] |
| - | [[Category: Muskett, F W]] | + | [[Category: Muskett FW]] |
| - | [[Category: Redpath, N T]] | + | [[Category: Redpath NT]] |
| - | [[Category: Taylor, R J]] | + | [[Category: Taylor RJ]] |
| - | [[Category: Veverka, V]] | + | [[Category: Veverka V]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Gp-130]]
| + | |
| - | [[Category: Interleukin]]
| + | |
| - | [[Category: Signaling]]
| + | |
| - | [[Category: Transcription]]
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| Structural highlights
Function
IL6_MOUSE 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. Acts on B-cells, T-cells, hepatocytes, hematopoietic progenitor cells and cells of the CNS. Required for the generation of T(H)17 cells. 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. It induces myeloma and plasmacytoma growth and induces nerve cells differentiation.[1]
Publication Abstract from PubMed
A number of secreted cytokines, such as interleukin-6 (IL-6), are attractive targets for the treatment of inflammatory diseases. We have determined the solution structure of mouse IL-6 to assess the functional significance of apparent differences in the receptor interaction sites (IL-6Ralpha and gp130) suggested by the fairly low degree of sequence similarity with human IL-6. Structure-based sequence alignment of mouse IL-6 and human IL-6 revealed surprising differences in the conservation of the two distinct gp130 binding sites (IIa and IIIa), which suggests a primacy for site III-mediated interactions in driving initial assembly of the IL-6/IL-6Ralpha/gp130 ternary complex. This is further supported by a series of direct binding experiments, which clearly demonstrate a high affinity IL-6/IL-6Ralpha-gp130 interaction via site III but only weak binding via site II. Collectively, our findings suggest a pathway for the evolution of the hexameric, IL-6/IL-6Ralpha/gp130 signaling complex and strategies for therapeutic targeting. We propose that the signaling complex originally involved specific interactions between IL-6 and IL-6Ralpha (site I) and between the D1 domain of gp130 and IL-6/IL-6Ralpha (site III), with the later inclusion of interactions between the D2 and D3 domains of gp130 and IL-6/IL-6Ralpha (site II) through serendipity. It seems likely that IL-6 signaling benefited from the evolution of a multipurpose, nonspecific protein interaction surface on gp130, now known as the cytokine binding homology region (site II contact surface), which fortuitously contributes to stabilization of the IL-6/IL-6Ralpha/gp130 signaling complex.
Conservation of functional sites on interleukin-6 and implications for evolution of signaling complex assembly and therapeutic intervention.,Veverka V, Baker T, Redpath NT, Carrington B, Muskett FW, Taylor RJ, Lawson AD, Henry AJ, Carr MD J Biol Chem. 2012 Nov 16;287(47):40043-50. doi: 10.1074/jbc.M112.405597. Epub, 2012 Oct 1. PMID:23027872[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ivanov II, McKenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR. The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell. 2006 Sep 22;126(6):1121-33. PMID:16990136 doi:http://dx.doi.org/10.1016/j.cell.2006.07.035
- ↑ Veverka V, Baker T, Redpath NT, Carrington B, Muskett FW, Taylor RJ, Lawson AD, Henry AJ, Carr MD. Conservation of functional sites on interleukin-6 and implications for evolution of signaling complex assembly and therapeutic intervention. J Biol Chem. 2012 Nov 16;287(47):40043-50. doi: 10.1074/jbc.M112.405597. Epub, 2012 Oct 1. PMID:23027872 doi:http://dx.doi.org/10.1074/jbc.M112.405597
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