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| | <StructureSection load='6o4o' size='340' side='right'caption='[[6o4o]], [[Resolution|resolution]] 1.62Å' scene=''> | | <StructureSection load='6o4o' size='340' side='right'caption='[[6o4o]], [[Resolution|resolution]] 1.62Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6o4o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=6O4O FirstGlance]. <br> | + | <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='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> | + | </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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL11 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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'>[http://proteopedia.org/fgij/fg.htm?mol=6o4o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o4o OCA], [http://pdbe.org/6o4o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o4o RCSB], [http://www.ebi.ac.uk/pdbsum/6o4o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o4o 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=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 == | | == Function == |
| - | [[http://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. | + | [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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Griffin, M D.W]] | + | [[Category: Griffin MDW]] |
| - | [[Category: Metcalfe, R D]] | + | [[Category: Metcalfe RD]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Interleukin]]
| + | |
| - | [[Category: Interleukin 11]]
| + | |
| - | [[Category: Protein binding]]
| + | |
| Structural highlights
Function
IL11_HUMAN Directly stimulates the proliferation of hematopoietic stem cells and megakaryocyte progenitor cells and induces megakaryocyte maturation resulting in increased platelet production.
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Metcalfe RD, Aizel K, Zlatic CO, Nguyen PM, Morton CJ, Lio DS, Cheng HC, Dobson RCJ, Parker MW, Gooley PR, Putoczki TL, Griffin MDW. The structure of the extracellular domains of human interleukin 11 alpha-receptor reveals mechanisms of cytokine engagement. J Biol Chem. 2020 Apr 24. pii: RA119.012351. doi: 10.1074/jbc.RA119.012351. PMID:32332100 doi:http://dx.doi.org/10.1074/jbc.RA119.012351
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