View source for 3nfp


==Crystal structure of the Fab fragment of therapeutic antibody daclizumab in complex with IL-2Ra (CD25) ectodomain==
<StructureSection load='3nfp' size='340' side='right' caption='[[3nfp]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3nfp]] is a 6 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=3NFP OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3NFP FirstGlance]. <br>
</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3iu3|3iu3]], [[3nfs|3nfs]]</td></tr>
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL2RA ([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=3nfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfp OCA], [http://pdbe.org/3nfp PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3nfp RCSB], [http://www.ebi.ac.uk/pdbsum/3nfp PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3nfp ProSAT]</span></td></tr>
</table>
== Disease ==
[[http://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Genetic variations in IL2RA are associated with susceptibility to diabetes mellitus insulin-dependent type 10 (IDDM10) [MIM:[http://omim.org/entry/601942 601942]]. A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical fetaures are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.<ref>PMID:17676041</ref>  
== Function ==
[[http://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Receptor for interleukin-2. 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nf/3nfp_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3nfp ConSurf].
<div style="clear:both"></div>
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== Publication Abstract from PubMed ==
Interleukin-2 (IL)-2 signaling plays a pivotal role in the activation of immune responses, and drugs that block this pathway have been shown to be effective for the immunosuppression in patients with organ transplantation to alleviate/eliminate allograft rejection. The first humanized monoclonal antibody (mAb) daclizumab falls into this category and shows high specificity and affinity against a key component of the IL-2 receptor complex, namely IL-2Ralpha. To reveal the molecular mechanism of the inhibition of the IL-2 signaling pathway by daclizumab, we determined the crystal structures of the daclizumab Fab in free form and in complex with the IL-2Ralpha ectodomain at 2.6 and 2.8 A resolution, respectively. The daclizumab Fab adopts a similar conformation in the presence or absence of the IL-2Ralpha ectodomain. The antigen-binding site of daclizumab is mainly composed of five complementarity determining regions (CDRs) that form a large positively charged surface depression and two flanking patches that are generally hydrophobic. The conformational epitope consists of several discontinuous segments of the IL-2Ralpha ectodomain, a large portion of which overlaps with the regions that interact with IL-2, suggesting that the binding of daclizumab to IL-2Ralpha would prevent the IL-2 binding to IL-2Ralpha and the subsequent formation of the IL-2/IL-2Ralphabetagamma(c) complex, and therefore block the IL-2 signaling pathway. These results also have implications for the design and development of improved mAb drugs targeting IL-2Ralpha.Cell Research advance online publication 7 September 2010; doi:10.1038/cr.2010.130.

Structural basis of immunosuppression by the therapeutic antibody daclizumab.,Yang H, Wang J, Du J, Zhong C, Zhang D, Guo H, Guo Y, Ding J Cell Res. 2010 Sep 7. PMID:20820193<ref>PMID:20820193</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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<div class="pdbe-citations 3nfp" style="background-color:#fffaf0;"></div>

==See Also==
*[[Interleukin receptor|Interleukin receptor]]
*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Human]]
[[Category: Ding, J]]
[[Category: Du, J]]
[[Category: Guo, Y]]
[[Category: Wang, J]]
[[Category: Yang, H]]
[[Category: Zhong, C]]
[[Category: Cd25]]
[[Category: Daclizumab]]
[[Category: Il-2ra]]
[[Category: Immune system]]
[[Category: Immune system-cytokine complex]]
[[Category: Therapeutic antibody]]
[[Category: Zenapax]]