View source for 7dr4


==Complex of anti-human IL-2 antibody and human IL-2==
<StructureSection load='7dr4' size='340' side='right'caption='[[7dr4]], [[Resolution|resolution]] 2.49&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7dr4]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7DR4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7DR4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.49&#8491;</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=7dr4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7dr4 OCA], [https://pdbe.org/7dr4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7dr4 RCSB], [https://www.ebi.ac.uk/pdbsum/7dr4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7dr4 ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/IL2_HUMAN IL2_HUMAN] Note=A chromosomal aberration involving IL2 is found in a form of T-cell acute lymphoblastic leukemia (T-ALL). Translocation t(4;16)(q26;p13) with involves TNFRSF17.
== Function ==
[https://www.uniprot.org/uniprot/IL2_HUMAN IL2_HUMAN] Produced by T-cells in response to antigenic or mitogenic stimulation, this protein is required for T-cell proliferation and other activities crucial to regulation of the immune response. Can stimulate B-cells, monocytes, lymphokine-activated killer cells, natural killer cells, and glioma cells.
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Immunotherapy via interleukin-2 (IL-2) mediated activation of anti-tumor immune response is a promising approach for cancer treatment. The multi-potent cytokine, IL-2 has a central role in immune cell activation and homeostasis. Since IL-2 preferentially activates immunosuppressive T regulatory cells by IL-2Ralpha dependent manner, blocking IL-2:IL-2Ralpha interaction is a key to amplify the IL-2 activity in effector T cells toward anti-tumor response. Anti-IL-2 monoclonal antibodies are good candidates to control the IL-2:IL-2Ralpha interaction. In a previous study, we developed a new IL-2Ralpha mimetic antibody, TCB2, and showed that the human IL-2(hIL-2):TCB2 complex can stimulate T effector cells specifically and elicit potent anti-cancer immunotherapeutic effect, especially when administered in combination with immune checkpoint inhibitors. To understand the molecular mechanism, we determined the crystal structure of TCB2-Fab in a complex with hIL-2 at 2.5 A resolution. Our structural analysis reveals that TCB2 binds to the central area of the hIL-2Ralpha binding region on hIL-2, and binding angle and epitope are different from previously known hIL-2Ralpha mimicking antibody NARA1 which recognizes the top part of hIL-2. TCB2 binding to hIL-2 also induces an allosteric effect that increases the affinity for the hetero-dimeric hIL-2 receptor, IL-2R(beta + gamma), on effector T cells.

Crystal structure of human interleukin-2 in complex with TCB2, a new antibody-drug candidate with antitumor activity.,Kim J, Lee JY, Park SY, Lee YJ, Kim MS Oncoimmunology. 2021 Mar 16;10(1):1899671. doi: 10.1080/2162402X.2021.1899671. PMID:33796411<ref>PMID:33796411</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7dr4" style="background-color:#fffaf0;"></div>

==See Also==
*[[Antibody 3D structures|Antibody 3D structures]]
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Kim JE]]
[[Category: Kim MS]]