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====
==IL23/IL23R/IL12Rb1 signaling complex==
<StructureSection load='6wdq' size='340' side='right'caption='[[6wdq]]' scene=''>
<StructureSection load='6wdq' size='340' side='right'caption='[[6wdq]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>
<table><tr><td colspan='2'>[[6wdq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WDQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WDQ FirstGlance]. <br>
</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=6wdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wdq OCA], [https://pdbe.org/6wdq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wdq RCSB], [https://www.ebi.ac.uk/pdbsum/6wdq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wdq ProSAT]</span></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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</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=6wdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wdq OCA], [https://pdbe.org/6wdq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wdq RCSB], [https://www.ebi.ac.uk/pdbsum/6wdq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wdq ProSAT]</span></td></tr>
</table>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interleukin-12 (IL-12) and IL-23 are heterodimeric cytokines that are produced by antigen-presenting cells to regulate the activation and differentiation of lymphocytes, and they share IL-12Rbeta1 as a receptor signaling subunit. We present a crystal structure of the quaternary IL-23 (IL-23p19/p40)/IL-23R/IL-12Rbeta1 complex, together with cryoelectron microscopy (cryo-EM) maps of the complete IL-12 (IL-12p35/p40)/IL-12Rbeta2/IL-12Rbeta1 and IL-23 receptor (IL-23R) complexes, which reveal "non-canonical" topologies where IL-12Rbeta1 directly engages the common p40 subunit. We targeted the shared IL-12Rbeta1/p40 interface to design a panel of IL-12 partial agonists that preserved interferon gamma (IFNgamma) induction by CD8(+) T cells but impaired cytokine production from natural killer (NK) cells in vitro. These cell-biased properties were recapitulated in vivo, where IL-12 partial agonists elicited anti-tumor immunity to MC-38 murine adenocarcinoma absent the NK-cell-mediated toxicity seen with wild-type IL-12. Thus, the structural mechanism of receptor sharing used by IL-12 family cytokines provides a protein interface blueprint for tuning this cytokine axis for therapeutics.
Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells.,Glassman CR, Mathiharan YK, Jude KM, Su L, Panova O, Lupardus PJ, Spangler JB, Ely LK, Thomas C, Skiniotis G, Garcia KC Cell. 2021 Feb 18;184(4):983-999.e24. doi: 10.1016/j.cell.2021.01.018. PMID:33606986<ref>PMID:33606986</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6wdq" style="background-color:#fffaf0;"></div>
==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Large Structures]]
[[Category: Z-disk]]
[[Category: Ely LK]]
[[Category: Garcia KC]]
[[Category: Glassman CR]]
[[Category: Jude KM]]
[[Category: Lupardus PJ]]
[[Category: Spangler JB]]
[[Category: Thomas C]]
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