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6o4o
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==The structure of human interleukin 11== | ==The structure of human interleukin 11== | ||
| - | <StructureSection load='6o4o' size='340' side='right'caption='[[6o4o]]' scene=''> | + | <StructureSection load='6o4o' size='340' side='right'caption='[[6o4o]], [[Resolution|resolution]] 1.62Å' 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=6O4O OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6o4o]] is a 1 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=6O4O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6O4O FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.62Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</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=6o4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o4o OCA], [https://pdbe.org/6o4o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6o4o RCSB], [https://www.ebi.ac.uk/pdbsum/6o4o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6o4o ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/IL11_HUMAN IL11_HUMAN] Directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Interleukin 11 (IL-11) activates multiple intracellular signalling pathways by forming a complex with its cell surface alpha-receptor, IL-11Ralpha, and the beta-subunit receptor, gp130. Dysregulated IL-11 signalling has been implicated in several diseases, including some cancers and fibrosis. Mutations in IL-11Ralpha that reduce signalling are also associated with hereditary cranial malformations. Here we present the first crystal structure of the extracellular domains of human IL-11Ralpha, and a structure of human IL-11 that reveals previously unresolved detail. Disease-associated mutations in IL-11Ralpha are generally distal to putative ligand binding sites. Molecular dynamics simulations showed that specific mutations destabilise IL-11Ralpha and may have indirect effects on the cytokine binding region. We show that IL-11 and IL-11Ralpha form a 1:1 complex with nanomolar affinity and present a model of the complex. Our results suggest that the thermodynamic and structural mechanisms of complex formation between IL-11 and IL-11Ralpha differ substantially from those previously reported for similar cytokines. This work reveals key determinants of the engagement of IL-11 by IL-11Ralpha that may be exploited in the development of strategies to modulate formation of the IL-11/IL-11Ralpha complex. | ||
| + | |||
| + | The structure of the extracellular domains of human interleukin 11 alpha-receptor reveals mechanisms of cytokine engagement.,Metcalfe RD, Aizel K, Zlatic CO, Nguyen PM, Morton CJ, Lio DS, Cheng HC, Dobson RCJ, Parker MW, Gooley PR, Putoczki TL, Griffin MDW J Biol Chem. 2020 Apr 24. pii: RA119.012351. doi: 10.1074/jbc.RA119.012351. PMID:32332100<ref>PMID:32332100</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6o4o" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Griffin MDW]] | [[Category: Griffin MDW]] | ||
[[Category: Metcalfe RD]] | [[Category: Metcalfe RD]] | ||
Current revision
The structure of human interleukin 11
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