4yue: Difference between revisions
From Proteopedia
Jump to navigationJump to search
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
''' | ==Mouse IL-2 Bound to S4B6 Fab Fragment== | ||
<StructureSection load='4yue' size='340' side='right' caption='[[4yue]], [[Resolution|resolution]] 2.19Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[4yue]] is a 3 chain structure. 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4YUE FirstGlance]. <br> | |||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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=4yue FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4yue OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4yue RCSB], [http://www.ebi.ac.uk/pdbsum/4yue PDBsum]</span></td></tr> | |||
</table> | |||
== 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. | |||
<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> | |||
</div> | |||
== References == | |||
[[Category: | <references/> | ||
[[Category: Spangler, J | __TOC__ | ||
[[Category: | </StructureSection> | ||
[[Category: | [[Category: Garcia, K C]] | ||
[[Category: Jude, K M]] | |||
[[Category: Spangler, J B]] | |||
[[Category: Antibody]] | |||
[[Category: Chemokine]] | |||
[[Category: Complex]] | |||
[[Category: Cytokine/immune system complex]] | |||
Revision as of 12:11, 1 July 2015
Mouse IL-2 Bound to S4B6 Fab Fragment
| ||||||||||||
