View source for 5lqb


==Complex structure of human IL2 mutant, Proleukin, with Fab fragment of NARA1 antibody==
<StructureSection load='5lqb' size='340' side='right'caption='[[5lqb]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5lqb]] is a 3 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=5LQB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5LQB 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]] 1.95&#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=5lqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lqb OCA], [https://pdbe.org/5lqb PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5lqb RCSB], [https://www.ebi.ac.uk/pdbsum/5lqb PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5lqb 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.
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== Publication Abstract from PubMed ==
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor alpha (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25. Association of NARA1 with IL-2 occurs with 10-fold higher affinity compared to CD25 and forms IL-2/NARA1 complexes, which, in vivo, preferentially stimulate CD8+ T cells while disfavoring CD25+ Tregs and improving the benefit-to-adverse effect ratio of IL-2. In two transplantable and one spontaneous metastatic melanoma model, IL-2/NARA1 complex immunotherapy resulted in efficient expansion of tumor-specific and polyclonal CD8+ T cells. These CD8+ T cells showed robust interferon-gamma production and expressed low levels of exhaustion markers programmed cell death protein-1, lymphocyte activation gene-3, and T cell immunoglobulin and mucin domain-3. These effects resulted in potent anticancer immune responses and prolonged survival in the tumor models. Collectively, our data demonstrate that NARA1 acts as a CD25-mimobody that confers selectivity and increased potency to IL-2 and warrant further assessment of NARA1 as a therapeutic.

Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2.,Arenas-Ramirez N, Zou C, Popp S, Zingg D, Brannetti B, Wirth E, Calzascia T, Kovarik J, Sommer L, Zenke G, Woytschak J, Regnier CH, Katopodis A, Boyman O Sci Transl Med. 2016 Nov 30;8(367):367ra166. PMID:27903862<ref>PMID:27903862</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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==See Also==
*[[Interleukin 3D structures|Interleukin 3D structures]]
== References ==
<references/>
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</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Wirth E]]
[[Category: Zou C]]