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| <StructureSection load='6wdp' size='340' side='right'caption='[[6wdp]], [[Resolution|resolution]] 2.01Å' scene=''> | | <StructureSection load='6wdp' size='340' side='right'caption='[[6wdp]], [[Resolution|resolution]] 2.01Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6wdp]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WDP FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WDP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WDP FirstGlance]. <br> |
| </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.01Å</td></tr> |
| <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL12RB1, IL12R, IL12RB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=6wdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wdp OCA], [https://pdbe.org/6wdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wdp RCSB], [https://www.ebi.ac.uk/pdbsum/6wdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wdp 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=6wdp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wdp OCA], [https://pdbe.org/6wdp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wdp RCSB], [https://www.ebi.ac.uk/pdbsum/6wdp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wdp ProSAT]</span></td></tr> |
| </table> | | </table> |
| == Disease ==
| |
| [[https://www.uniprot.org/uniprot/I12R1_HUMAN I12R1_HUMAN]] Primary biliary cholangitis;Mendelian susceptibility to mycobacterial diseases due to complete IL12RB1 deficiency. The disease is caused by variants affecting the gene represented in this entry.
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| == Function ==
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| [[https://www.uniprot.org/uniprot/I12R1_HUMAN I12R1_HUMAN]] Functions as an interleukin receptor which binds interleukin-12 with low affinity and is involved in IL12 transduction. Associated with IL12RB2 it forms a functional, high affinity receptor for IL12. Associates also with IL23R to form the interleukin-23 receptor which functions in IL23 signal transduction probably through activation of the Jak-Stat signaling cascade.<ref>PMID:12023369</ref>
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| <div style="background-color:#fffaf0;">
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| == 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.
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| 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>
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| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6wdp" style="background-color:#fffaf0;"></div>
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| == References ==
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| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]]
| |
| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Garcia, K C]] | | [[Category: Garcia KC]] |
| [[Category: Jude, K M]] | | [[Category: Jude KM]] |
| [[Category: Spangler, J B]] | | [[Category: Spangler JB]] |
| [[Category: Thomas, C]] | | [[Category: Thomas C]] |
| [[Category: Cytokine receptor]]
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| [[Category: Signaling protein]]
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