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5lqb

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Complex structure of human IL2 mutant, Proleukin, with Fab fragment of NARA1 antibody

Structural highlights

5lqb is a 3 chain structure with sequence from Homo sapiens and Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.95Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

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

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.

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^[1]

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

References

↑ 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. Improved cancer immunotherapy by a CD25-mimobody conferring selectivity to human interleukin-2. Sci Transl Med. 2016 Nov 30;8(367):367ra166. PMID:27903862 doi:http://dx.doi.org/10.1126/scitranslmed.aag3187

1 Structural highlights
2 Disease
3 Function
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5lqb"

Categories: Homo sapiens | Large Structures | Mus musculus | Wirth E | Zou C

@@ Line 3: / Line 3: @@
 <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 [http://en.wikipedia.org/wiki/Human Human] and [http://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 [http://proteopedia.org/fgij/fg.htm?mol=5LQB FirstGlance]. <br>
+<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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5lqb FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5lqb OCA], [http://pdbe.org/5lqb PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5lqb RCSB], [http://www.ebi.ac.uk/pdbsum/5lqb PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5lqb ProSAT]</span></td></tr>
+</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 ==
-[[http://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.
+[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 ==
-[[http://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.
+[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 ==
@@ Line 26: / Line 27: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[Category: Large Structures]]
 [[Category: Mus musculus]]
-[[Category: Wirth, E]]
+[[Category: Wirth E]]
-[[Category: Zou, C]]
+[[Category: Zou C]]
-[[Category: Anti-il2]]
-[[Category: Cytokine]]
-[[Category: Il2]]
-[[Category: Nara1]]
-[[Category: Proleukin]]

5lqb

From Proteopedia

Current revision

Complex structure of human IL2 mutant, Proleukin, with Fab fragment of NARA1 antibody

Structural highlights

Disease

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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