8qy5
From Proteopedia
(Difference between revisions)
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<table><tr><td colspan='2'>[[8qy5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QY5 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8qy5]] is a 6 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8QY5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8QY5 FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.1Å</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]] 3.1Å</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=8qy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qy5 OCA], [https://pdbe.org/8qy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qy5 RCSB], [https://www.ebi.ac.uk/pdbsum/8qy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qy5 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=8qy5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8qy5 OCA], [https://pdbe.org/8qy5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8qy5 RCSB], [https://www.ebi.ac.uk/pdbsum/8qy5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8qy5 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| - | == Disease == | ||
| - | [https://www.uniprot.org/uniprot/IL6_HUMAN IL6_HUMAN] Genetic variations in IL6 are associated with susceptibility to rheumatoid arthritis systemic juvenile (RASJ) [MIM:[https://omim.org/entry/604302 604302]. An inflammatory articular disorder with systemic-onset beginning before the age of 16. It represents a subgroup of juvenile arthritis associated with severe extraarticular features and occasionally fatal complications. During active phases of the disorder, patients display a typical daily spiking fever, an evanescent macular rash, lymphadenopathy, hepatosplenomegaly, serositis, myalgia and arthritis. Note=A IL6 promoter polymorphism is associated with a lifetime risk of development of Kaposi sarcoma in HIV-infected men. | ||
== Function == | == Function == | ||
| - | [https://www.uniprot.org/uniprot/ | + | [https://www.uniprot.org/uniprot/IL6RB_MOUSE IL6RB_MOUSE] Signal-transducing molecule. The receptor systems for IL6, LIF, OSM, CNTF, IL11, CTF1 and BSF3 can utilize gp130 for initiating signal transmission. Binds to IL6/IL6R (alpha chain) complex, resulting in the formation of high-affinity IL6 binding sites, and transduces the signal. Does not bind IL6. May have a role in embryonic development. |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | IL-11 and IL-6 activate signalling via assembly of the cell surface receptor gp130; however, it is unclear how signals are transmitted across the membrane to instruct cellular responses. Here we solve the cryoEM structure of the IL-11 receptor recognition complex to discover how differences in gp130-binding interfaces may drive signalling outcomes. We explore how mutations in the IL6ST gene encoding for gp130, which cause severe immune deficiencies in humans, impair signalling without blocking cytokine binding. We use cryoEM to solve structures of both IL-11 and IL-6 complexes with a mutant form of gp130 associated with human disease. Together with molecular dynamics simulations, we show that the disease-associated variant led to an increase in flexibility including motion within the cytokine-binding core and increased distance between extracellular domains. However, these distances are minimized as the transmembrane helix exits the membrane, suggesting a stringency in geometry for signalling and dimmer switch mode of action. | ||
| + | |||
| + | Structural insights into IL-11-mediated signalling and human IL6ST variant-associated immunodeficiency.,Gardner S, Jin Y, Fyfe PK, Voisin TB, Bellon JS, Pohler E, Piehler J, Moraga I, Bubeck D Nat Commun. 2024 Mar 7;15(1):2071. doi: 10.1038/s41467-024-46235-6. PMID:38453915<ref>PMID:38453915</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8qy5" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Current revision
Structure of interleukin 6.
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