4yqx
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Mouse IL-2 Bound to JES6-1 scFv Fragment== | |
| + | <StructureSection load='4yqx' size='340' side='right'caption='[[4yqx]], [[Resolution|resolution]] 2.83Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <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='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='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'>[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> | ||
| + | == Function == | ||
| + | [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;"> | ||
| + | == 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<ref>PMID:25992858</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 4yqx" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | |
| - | [[Category: Garcia | + | ==See Also== |
| - | [[Category: Luca | + | *[[Antibody 3D structures|Antibody 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/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Mus musculus]] | ||
| + | [[Category: Rattus norvegicus]] | ||
| + | [[Category: Garcia KC]] | ||
| + | [[Category: Jude KM]] | ||
| + | [[Category: Luca VC]] | ||
| + | [[Category: Spangler JB]] | ||
Current revision
Mouse IL-2 Bound to JES6-1 scFv Fragment
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