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3nfp

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{{STRUCTURE_3nfp| PDB=3nfp | SCENE= }}
 
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===Crystal structure of the Fab fragment of therapeutic antibody daclizumab in complex with IL-2Ra (CD25) ectodomain===
 
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{{ABSTRACT_PUBMED_20820193}}
 
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==Disease==
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==Crystal structure of the Fab fragment of therapeutic antibody daclizumab in complex with IL-2Ra (CD25) ectodomain==
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[[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>
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<StructureSection load='3nfp' size='340' side='right'caption='[[3nfp]], [[Resolution|resolution]] 2.86&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[3nfp]] is a 6 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=3NFP OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3NFP FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.86&#8491;</td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3nfp FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3nfp OCA], [https://pdbe.org/3nfp PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3nfp RCSB], [https://www.ebi.ac.uk/pdbsum/3nfp PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3nfp ProSAT]</span></td></tr>
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</table>
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== Disease ==
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[https://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:[https://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>
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== Function ==
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[https://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN] Receptor for interleukin-2.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/nf/3nfp_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</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].
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<div style="clear:both"></div>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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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.
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==Function==
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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>
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[[http://www.uniprot.org/uniprot/IL2RA_HUMAN IL2RA_HUMAN]] Receptor for interleukin-2.
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==About this Structure==
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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[[3nfp]] is a 6 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3NFP OCA].
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</div>
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<div class="pdbe-citations 3nfp" style="background-color:#fffaf0;"></div>
==See Also==
==See Also==
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*[[Interleukin receptor|Interleukin receptor]]
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*[[Interleukin receptor 3D structures|Interleukin receptor 3D structures]]
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*[[Monoclonal Antibody|Monoclonal Antibody]]
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*[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]]
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== References ==
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==Reference==
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<references/>
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<ref group="xtra">PMID:020820193</ref><references group="xtra"/><references/>
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__TOC__
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
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[[Category: Ding, J.]]
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[[Category: Large Structures]]
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[[Category: Du, J.]]
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[[Category: Ding J]]
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[[Category: Guo, Y.]]
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[[Category: Du J]]
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[[Category: Wang, J.]]
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[[Category: Guo Y]]
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[[Category: Yang, H.]]
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[[Category: Wang J]]
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[[Category: Zhong, C.]]
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[[Category: Yang H]]
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[[Category: Cd25]]
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[[Category: Zhong C]]
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[[Category: Daclizumab]]
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[[Category: Il-2ra]]
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[[Category: Immune system]]
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[[Category: Immune system-cytokine complex]]
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[[Category: Therapeutic antibody]]
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[[Category: Zenapax]]
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Current revision

Crystal structure of the Fab fragment of therapeutic antibody daclizumab in complex with IL-2Ra (CD25) ectodomain

PDB ID 3nfp

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