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==Crystal Structure of Receptor-Fab Complex==
==Crystal Structure of Receptor-Fab Complex==
<StructureSection load='4jzj' size='340' side='right' caption='[[4jzj]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
<StructureSection load='4jzj' size='340' side='right' caption='[[4jzj]], [[Resolution|resolution]] 2.80&Aring;' scene=''>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUC:ALPHA-L-FUCOSE'>FUC</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL3RA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL3RA ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jzj OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4jzj RCSB], [http://www.ebi.ac.uk/pdbsum/4jzj PDBsum]</span></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4jzj FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jzj OCA], [http://pdbe.org/4jzj PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jzj RCSB], [http://www.ebi.ac.uk/pdbsum/4jzj PDBsum]</span></td></tr>
</table>
</table>
== Function ==
== Function ==
[[http://www.uniprot.org/uniprot/IL3RA_HUMAN IL3RA_HUMAN]] This is a receptor for interleukin-3.  
[[http://www.uniprot.org/uniprot/IL3RA_HUMAN IL3RA_HUMAN]] This is a receptor for interleukin-3.  
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Interleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Here, we report the crystal structure of the IL-3 receptor alpha chain (IL3Ralpha) in complex with the anti-leukemia antibody CSL362 that reveals the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5, and IL-13 receptors, adopting unique "open" and classical "closed" conformations. Although extensive mutational analyses of the NTD epitope of CSL362 show minor overlap with the IL-3 binding site, CSL362 only inhibits IL-3 binding to the closed conformation, indicating alternative mechanisms for blocking IL-3 signaling. Significantly, whereas "open-like" IL3Ralpha mutants can simultaneously bind IL-3 and CSL362, CSL362 still prevents the assembly of a higher-order IL-3 receptor-signaling complex. The discovery of open forms of cytokine receptors provides the framework for development of potent antibodies that can achieve a "double hit" cytokine receptor blockade.
Dual mechanism of interleukin-3 receptor blockade by an anti-cancer antibody.,Broughton SE, Hercus TR, Hardy MP, McClure BJ, Nero TL, Dottore M, Huynh H, Braley H, Barry EF, Kan WL, Dhagat U, Scotney P, Hartman D, Busfield SJ, Owczarek CM, Nash AD, Wilson NJ, Parker MW, Lopez AF Cell Rep. 2014 Jul 24;8(2):410-9. doi: 10.1016/j.celrep.2014.06.038. Epub 2014, Jul 17. PMID:25043189<ref>PMID:25043189</ref>
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4jzj" style="background-color:#fffaf0;"></div>
==See Also==
*[[Interleukin receptor|Interleukin receptor]]
== References ==
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>

Revision as of 22:15, 10 May 2016

Crystal Structure of Receptor-Fab ComplexCrystal Structure of Receptor-Fab Complex

Structural highlights

4jzj is a 6 chain structure with sequence from Human and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:, , , , ,
Gene:IL3RA (HUMAN)
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum

Function

[IL3RA_HUMAN] This is a receptor for interleukin-3.

Publication Abstract from PubMed

Interleukin-3 (IL-3) is an activated T cell product that bridges innate and adaptive immunity and contributes to several immunopathologies. Here, we report the crystal structure of the IL-3 receptor alpha chain (IL3Ralpha) in complex with the anti-leukemia antibody CSL362 that reveals the N-terminal domain (NTD), a domain also present in the granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-5, and IL-13 receptors, adopting unique "open" and classical "closed" conformations. Although extensive mutational analyses of the NTD epitope of CSL362 show minor overlap with the IL-3 binding site, CSL362 only inhibits IL-3 binding to the closed conformation, indicating alternative mechanisms for blocking IL-3 signaling. Significantly, whereas "open-like" IL3Ralpha mutants can simultaneously bind IL-3 and CSL362, CSL362 still prevents the assembly of a higher-order IL-3 receptor-signaling complex. The discovery of open forms of cytokine receptors provides the framework for development of potent antibodies that can achieve a "double hit" cytokine receptor blockade.

Dual mechanism of interleukin-3 receptor blockade by an anti-cancer antibody.,Broughton SE, Hercus TR, Hardy MP, McClure BJ, Nero TL, Dottore M, Huynh H, Braley H, Barry EF, Kan WL, Dhagat U, Scotney P, Hartman D, Busfield SJ, Owczarek CM, Nash AD, Wilson NJ, Parker MW, Lopez AF Cell Rep. 2014 Jul 24;8(2):410-9. doi: 10.1016/j.celrep.2014.06.038. Epub 2014, Jul 17. PMID:25043189[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. ↑ Broughton SE, Hercus TR, Hardy MP, McClure BJ, Nero TL, Dottore M, Huynh H, Braley H, Barry EF, Kan WL, Dhagat U, Scotney P, Hartman D, Busfield SJ, Owczarek CM, Nash AD, Wilson NJ, Parker MW, Lopez AF. Dual mechanism of interleukin-3 receptor blockade by an anti-cancer antibody. Cell Rep. 2014 Jul 24;8(2):410-9. doi: 10.1016/j.celrep.2014.06.038. Epub 2014, Jul 17. PMID:25043189 doi:http://dx.doi.org/10.1016/j.celrep.2014.06.038

4jzj, resolution 2.80Å

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