6o4p
From Proteopedia
(Difference between revisions)
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==The crystal structure of the interleukin 11 alpha receptor== | ==The crystal structure of the interleukin 11 alpha receptor== | ||
| - | <StructureSection load='6o4p' size='340' side='right'caption='[[6o4p]]' scene=''> | + | <StructureSection load='6o4p' size='340' side='right'caption='[[6o4p]], [[Resolution|resolution]] 3.43Å' 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=6O4P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6O4P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6o4p]] is a 2 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=6O4P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6O4P FirstGlance]. <br> |
| - | </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=6o4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o4p OCA], [http://pdbe.org/6o4p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o4p RCSB], [http://www.ebi.ac.uk/pdbsum/6o4p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o4p ProSAT]</span></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL11RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=6o4p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6o4p OCA], [http://pdbe.org/6o4p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6o4p RCSB], [http://www.ebi.ac.uk/pdbsum/6o4p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6o4p ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/I11RA_HUMAN I11RA_HUMAN]] Craniosynostosis-dental anomalies. The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/I11RA_HUMAN I11RA_HUMAN]] Receptor for interleukin-11. The receptor systems for IL6, LIF, OSM, CNTF, IL11 and CT1 can utilize IL6ST for initiating signal transmission. The IL11/IL11RA/IL6ST complex may be involved in the control of proliferation and/or differentiation of skeletogenic progenitor or other mesenchymal cells. Essential for the normal development of craniofacial bones and teeth. Restricts suture fusion and tooth number.<ref>PMID:21741611</ref> | ||
| + | <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 6o4p" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Human]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Aizel K]] | + | [[Category: Aizel, K]] |
| - | [[Category: Griffin | + | [[Category: Griffin, M D.W]] |
| - | [[Category: Metcalfe | + | [[Category: Metcalfe, R D]] |
| + | [[Category: Cytokine]] | ||
| + | [[Category: Interleukin]] | ||
| + | [[Category: Protein binding]] | ||
| + | [[Category: Receptor]] | ||
Revision as of 06:53, 25 June 2020
The crystal structure of the interleukin 11 alpha receptor
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