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4yue

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Current revision (08:06, 27 September 2023) (edit) (undo)
 
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'''Unreleased structure'''
 
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The entry 4yue is ON HOLD until Paper Publication
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==Mouse IL-2 Bound to S4B6 Fab Fragment==
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<StructureSection load='4yue' size='340' side='right'caption='[[4yue]], [[Resolution|resolution]] 2.19&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[4yue]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4YUE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4YUE 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]] 2.194&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></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=4yue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yue OCA], [https://pdbe.org/4yue PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4yue RCSB], [https://www.ebi.ac.uk/pdbsum/4yue PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4yue ProSAT]</span></td></tr>
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</table>
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== Function ==
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[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.
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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Authors: Spangler, J.B., Jude, K.M., Garcia, K.C.
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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>
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Description:
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[Category: Unreleased Structures]]
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</div>
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[[Category: Spangler, J.B]]
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<div class="pdbe-citations 4yue" style="background-color:#fffaf0;"></div>
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[[Category: Jude, K.M]]
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[[Category: Garcia, K.C]]
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==See Also==
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*[[Interleukin 3D structures|Interleukin 3D structures]]
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== References ==
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<references/>
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__TOC__
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</StructureSection>
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[[Category: Large Structures]]
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[[Category: Mus musculus]]
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[[Category: Garcia KC]]
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[[Category: Jude KM]]
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[[Category: Spangler JB]]

Current revision

Mouse IL-2 Bound to S4B6 Fab Fragment

PDB ID 4yue

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