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| | <StructureSection load='4yqx' size='340' side='right'caption='[[4yqx]], [[Resolution|resolution]] 2.83Å' scene=''> | | <StructureSection load='4yqx' size='340' side='right'caption='[[4yqx]], [[Resolution|resolution]] 2.83Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4yqx]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YQX OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YQX FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4yqx]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus] and [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YQX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YQX FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.826Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Il2, Il-2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4yqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yqx OCA], [http://pdbe.org/4yqx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4yqx RCSB], [http://www.ebi.ac.uk/pdbsum/4yqx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4yqx 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=4yqx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yqx OCA], [https://pdbe.org/4yqx PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yqx RCSB], [https://www.ebi.ac.uk/pdbsum/4yqx PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yqx ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL2_MOUSE IL2_MOUSE]] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. | + | [https://www.uniprot.org/uniprot/IL2_MOUSE IL2_MOUSE] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| | *[[Interleukin 3D structures|Interleukin 3D structures]] | | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Buffalo rat]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Garcia, K C]] | + | [[Category: Rattus norvegicus]] |
| - | [[Category: Jude, K M]] | + | [[Category: Garcia KC]] |
| - | [[Category: Luca, V C]] | + | [[Category: Jude KM]] |
| - | [[Category: Spangler, J B]] | + | [[Category: Luca VC]] |
| - | [[Category: Antibody]] | + | [[Category: Spangler JB]] |
| - | [[Category: Chemokine]]
| + | |
| - | [[Category: Complex]]
| + | |
| - | [[Category: Cytokine-immune system complex]]
| + | |
| Structural highlights
Function
IL2_MOUSE Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.
Publication Abstract from PubMed
Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates immune cell homeostasis and has been used to treat a range of disorders including cancer and autoimmune disease. IL-2 signals via interleukin-2 receptor-beta (IL-2Rbeta):IL-2Rgamma heterodimers on cells expressing high (regulatory T cells, Treg) or low (effector cells) amounts of IL-2Ralpha (CD25). When complexed with IL-2, certain anti-cytokine antibodies preferentially stimulate expansion of Treg (JES6-1) or effector (S4B6) cells, offering a strategy for targeted disease therapy. We found that JES6-1 sterically blocked the IL-2:IL-2Rbeta and IL-2:IL-2Rgamma interactions, but also allosterically lowered the IL-2:IL-2Ralpha affinity through a "triggered exchange" mechanism favoring IL-2Ralpha(hi) Treg cells, creating a positive feedback loop for IL-2Ralpha(hi) cell activation. Conversely, S4B6 sterically blocked the IL-2:IL-2Ralpha interaction, while also conformationally stabilizing the IL-2:IL-2Rbeta interaction, thus stimulating all IL-2-responsive immune cells, particularly IL-2Rbeta(hi) effector cells. These insights provide a molecular blueprint for engineering selectively potentiating therapeutic antibodies.
Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms.,Spangler JB, Tomala J, Luca VC, Jude KM, Dong S, Ring AM, Votavova P, Pepper M, Kovar M, Garcia KC Immunity. 2015 May 19;42(5):815-25. doi: 10.1016/j.immuni.2015.04.015. PMID:25992858[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Spangler JB, Tomala J, Luca VC, Jude KM, Dong S, Ring AM, Votavova P, Pepper M, Kovar M, Garcia KC. Antibodies to Interleukin-2 Elicit Selective T Cell Subset Potentiation through Distinct Conformational Mechanisms. Immunity. 2015 May 19;42(5):815-25. doi: 10.1016/j.immuni.2015.04.015. PMID:25992858 doi:http://dx.doi.org/10.1016/j.immuni.2015.04.015
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