5lqb: Difference between revisions

Line 1:

~~'''Unreleased structure'''~~

~~The entry~~ 5lqb is ~~ON HOLD until Paper~~ Publication

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

== Structural highlights ==

<table><tr><td colspan='2'>[[5lqb]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/ ] 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://oca.weizmann.ac.il/oca-docs/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://oca.weizmann.ac.il/oca-docs/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>

</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.

== 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.

== 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.

~~Authors:~~ Zou, C., Wirth, E.

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>

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

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

[[Category: ~~Unreleased Structures~~]]

</div>

== References ==

__TOC__

</StructureSection>

[[Category: Mus musculus]]

[[Category: Wirth, E]]

[[Category: Zou, C]]

[[Category: Anti-il2]]

[[Category: Cytokine]]

[[Category: Il2]]

[[Category: Nara1]]

[[Category: Proleukin]]

Navigation menu

Page actions

Page actions

Personal tools

Navigation

Search

Tools

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 5lqb is ON HOLD  until Paper Publication
+==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 [http://en.wikipedia.org/wiki/ ] 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://oca.weizmann.ac.il/oca-docs/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://oca.weizmann.ac.il/oca-docs/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>
+</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.
+== 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.
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Zou, C., Wirth, E.
+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>
-Description: Complex structure of human IL2 mutant, Proleukin, with Fab fragment of NARA1 antibody
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
+<div class="pdbe-citations 5lqb" style="background-color:#fffaf0;"></div>
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Mus musculus]]
 [[Category: Wirth, E]]
 [[Category: Zou, C]]
+[[Category: Anti-il2]]
+[[Category: Cytokine]]
+[[Category: Il2]]
+[[Category: Nara1]]
+[[Category: Proleukin]]