6x93: Difference between revisions
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==== | ==Interleukin-10 signaling complex with IL-10RA and IL-10RB== | ||
<StructureSection load='6x93' size='340' side='right'caption='[[6x93]]' scene=''> | <StructureSection load='6x93' size='340' side='right'caption='[[6x93]], [[Resolution|resolution]] 3.50Å' 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'>[[6x93]] is a 6 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=6X93 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6X93 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=6x93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x93 OCA], [https://pdbe.org/6x93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x93 RCSB], [https://www.ebi.ac.uk/pdbsum/6x93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x93 ProSAT]</span></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]] 3.5Å</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=6x93 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6x93 OCA], [https://pdbe.org/6x93 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6x93 RCSB], [https://www.ebi.ac.uk/pdbsum/6x93 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6x93 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Interleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. The hexameric structure shows how IL-10 and IL-10Ralpha form a composite surface to engage the shared signaling receptor IL-10Rbeta, enabling the design of partial agonists. IL-10 variants with a range of IL-10Rbeta binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity. Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8(+) T cells, thereby uncoupling the major opposing functions of IL-10. These results provide a mechanistic blueprint for tuning the pleiotropic actions of IL-10. | |||
Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.,Saxton RA, Tsutsumi N, Su LL, Abhiraman GC, Mohan K, Henneberg LT, Aduri NG, Gati C, Garcia KC Science. 2021 Mar 19;371(6535):eabc8433. doi: 10.1126/science.abc8433. PMID:33737461<ref>PMID:33737461</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 6x93" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Garcia KC]] | ||
[[Category: Gati C]] | |||
[[Category: Saxton RA]] | |||
[[Category: Tsutsumi N]] | |||
Latest revision as of 11:28, 17 October 2024
Interleukin-10 signaling complex with IL-10RA and IL-10RBInterleukin-10 signaling complex with IL-10RA and IL-10RB
Structural highlights
Publication Abstract from PubMedInterleukin-10 (IL-10) is an immunoregulatory cytokine with both anti-inflammatory and immunostimulatory properties and is frequently dysregulated in disease. We used a structure-based approach to deconvolute IL-10 pleiotropy by determining the structure of the IL-10 receptor (IL-10R) complex by cryo-electron microscopy at a resolution of 3.5 angstroms. The hexameric structure shows how IL-10 and IL-10Ralpha form a composite surface to engage the shared signaling receptor IL-10Rbeta, enabling the design of partial agonists. IL-10 variants with a range of IL-10Rbeta binding strengths uncovered substantial differences in response thresholds across immune cell populations, providing a means of manipulating IL-10 cell type selectivity. Some variants displayed myeloid-biased activity by suppressing macrophage activation without stimulating inflammatory CD8(+) T cells, thereby uncoupling the major opposing functions of IL-10. These results provide a mechanistic blueprint for tuning the pleiotropic actions of IL-10. Structure-based decoupling of the pro- and anti-inflammatory functions of interleukin-10.,Saxton RA, Tsutsumi N, Su LL, Abhiraman GC, Mohan K, Henneberg LT, Aduri NG, Gati C, Garcia KC Science. 2021 Mar 19;371(6535):eabc8433. doi: 10.1126/science.abc8433. PMID:33737461[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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