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6wdp

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Interleukin 12 receptor subunit beta-1

Structural highlights

6wdp is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	,
Gene:	IL12RB1, IL12R, IL12RB (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[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

[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.^[1]

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^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Parham C, Chirica M, Timans J, Vaisberg E, Travis M, Cheung J, Pflanz S, Zhang R, Singh KP, Vega F, To W, Wagner J, O'Farrell AM, McClanahan T, Zurawski S, Hannum C, Gorman D, Rennick DM, Kastelein RA, de Waal Malefyt R, Moore KW. A receptor for the heterodimeric cytokine IL-23 is composed of IL-12Rbeta1 and a novel cytokine receptor subunit, IL-23R. J Immunol. 2002 Jun 1;168(11):5699-708. PMID:12023369
↑ Glassman CR, Mathiharan YK, Jude KM, Su L, Panova O, Lupardus PJ, Spangler JB, Ely LK, Thomas C, Skiniotis G, Garcia KC. Structural basis for IL-12 and IL-23 receptor sharing reveals a gateway for shaping actions on T versus NK cells. Cell. 2021 Feb 18;184(4):983-999.e24. doi: 10.1016/j.cell.2021.01.018. PMID:33606986 doi:http://dx.doi.org/10.1016/j.cell.2021.01.018

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/6wdp"

@@ Line 3: / Line 3: @@
 <StructureSection load='6wdp' size='340' side='right'caption='[[6wdp]], [[Resolution|resolution]] 2.01&Aring;' scene=''>
 == Structural highlights ==
-<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>
+<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>
 </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='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='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>
@@ Line 24: / Line 25: @@
 __TOC__
 </StructureSection>
+[[Category: Human]]
 [[Category: Large Structures]]
 [[Category: Garcia, K C]]

6wdp

From Proteopedia

Current revision

Interleukin 12 receptor subunit beta-1

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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