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6wdp
From Proteopedia
(Difference between revisions)
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==Interleukin 12 receptor subunit beta-1== | ==Interleukin 12 receptor subunit beta-1== | ||
| - | <StructureSection load='6wdp' size='340' side='right'caption='[[6wdp]]' scene=''> | + | <StructureSection load='6wdp' size='340' side='right'caption='[[6wdp]], [[Resolution|resolution]] 2.01Å' 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=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'>[[6wdp]] is a 1 chain structure. 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='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> | + | </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> | ||
</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. | ||
| + | == Function == | ||
| + | [[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> | ||
| + | <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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wdp" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Garcia | + | [[Category: Garcia, K C]] |
| - | [[Category: Jude | + | [[Category: Jude, K M]] |
| - | [[Category: Spangler | + | [[Category: Spangler, J B]] |
| - | [[Category: Thomas C]] | + | [[Category: Thomas, C]] |
| + | [[Category: Cytokine receptor]] | ||
| + | [[Category: Signaling protein]] | ||
Revision as of 14:57, 3 March 2021
Interleukin 12 receptor subunit beta-1
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