7z0l
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7z0l]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Z0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z0L FirstGlance]. <br> | <table><tr><td colspan='2'>[[7z0l]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7Z0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7Z0L FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 4Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=7z0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z0l OCA], [https://pdbe.org/7z0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z0l RCSB], [https://www.ebi.ac.uk/pdbsum/7z0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z0l 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=7z0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7z0l OCA], [https://pdbe.org/7z0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7z0l RCSB], [https://www.ebi.ac.uk/pdbsum/7z0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7z0l ProSAT]</span></td></tr> | ||
</table> | </table> | ||
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Interleukin 27 (IL-27) is a heterodimeric cytokine that elicits potent immunosuppressive responses. Comprised of EBI3 and p28 subunits, IL-27 binds GP130 and IL-27Ralpha receptor chains to activate the JAK/STAT signaling cascade. However, how these receptors recognize IL-27 and form a complex capable of phosphorylating JAK proteins remains unclear. Here, we used cryo electron microscopy (cryoEM) and AlphaFold modeling to solve the structure of the IL-27 receptor recognition complex. Our data show how IL-27 serves as a bridge connecting IL-27Ralpha (domains 1-2) with GP130 (domains 1-3) to initiate signaling. While both receptors contact the p28 component of the heterodimeric cytokine, EBI3 stabilizes the complex by binding a positively charged surface of IL-27Ralpha and Domain 1 of GP130. We find that assembly of the IL-27 receptor recognition complex is distinct from both IL-12 and IL-6 cytokine families and provides a mechanistic blueprint for tuning IL-27 pleiotropic actions. | Interleukin 27 (IL-27) is a heterodimeric cytokine that elicits potent immunosuppressive responses. Comprised of EBI3 and p28 subunits, IL-27 binds GP130 and IL-27Ralpha receptor chains to activate the JAK/STAT signaling cascade. However, how these receptors recognize IL-27 and form a complex capable of phosphorylating JAK proteins remains unclear. Here, we used cryo electron microscopy (cryoEM) and AlphaFold modeling to solve the structure of the IL-27 receptor recognition complex. Our data show how IL-27 serves as a bridge connecting IL-27Ralpha (domains 1-2) with GP130 (domains 1-3) to initiate signaling. While both receptors contact the p28 component of the heterodimeric cytokine, EBI3 stabilizes the complex by binding a positively charged surface of IL-27Ralpha and Domain 1 of GP130. We find that assembly of the IL-27 receptor recognition complex is distinct from both IL-12 and IL-6 cytokine families and provides a mechanistic blueprint for tuning IL-27 pleiotropic actions. | ||
| - | Structural insights into the assembly and activation of the IL-27 signaling complex.,Jin Y, Fyfe PK, Gardner S, Wilmes S, Bubeck D, Moraga I EMBO Rep. 2022 | + | Structural insights into the assembly and activation of the IL-27 signaling complex.,Jin Y, Fyfe PK, Gardner S, Wilmes S, Bubeck D, Moraga I EMBO Rep. 2022 Oct 6;23(10):e55450. doi: 10.15252/embr.202255450. Epub 2022 Aug , 3. PMID:35920255<ref>PMID:35920255</ref> |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | </div> | ||
<div class="pdbe-citations 7z0l" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 7z0l" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Interleukin 3D structures|Interleukin 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
IL-27 signalling complex
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