3qb1 - Revision history

OCA at 11:39, 14 March 2024

OCA — Thu, 14 Mar 2024 11:39:14 GMT

←Older revision		Revision as of 11:39, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3qb1' size='340' side='right'caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3qb1' size='340' side='right'caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qb1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QB1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qb1]] is a 8 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=3QB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QB1 FirstGlance]. <br>
-	</td></tr><tr id='~~related~~'><td class="sblockLbl"><b>[[~~Related_structure~~\|~~Related~~:]]</b></td><td class="sblockDat"~~><div style='overflow: auto; max-height: 3em;'>[[3qaz\|3qaz]], [[3ink\|3ink]], [[1m47\|1m47]]</div></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]] 3.1Å</td></tr>
-	~~<tr~~ id~~='gene'><td class~~="~~sblockLbl~~">~~<b>~~[[~~Gene~~\|~~Gene:~~]]~~</b></td><td class="sblockDat">IL2 ([https://www~~.~~ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info~~&~~srchmode=5&id=9606 HUMAN])~~</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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [https://pdbe.org/3qb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [https://www.ebi.ac.uk/pdbsum/3qb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb1 ProSAT]</span></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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [https://pdbe.org/3qb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [https://www.ebi.ac.uk/pdbsum/3qb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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.	+	[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 ==		== 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.	+	[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 ==~~	+
-	The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells. Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary 'high affinity' receptor complex consisting of IL-2, IL-2Ralpha (termed CD25), IL-2Rbeta and IL-2Rgamma. Naive T cells express only a low density of IL-2Rbeta and IL-2Rgamma, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2Rbeta and IL-2Rgamma. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 'superkine' (also called super-2) with increased binding affinity for IL-2Rbeta. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2Rbeta binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo, and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.	+
-		+
-	Exploiting a natural conformational switch to engineer an interleukin-2 'superkine',Levin AM, Bates DL, Ring AM, Krieg C, Lin JT, Su L, Moraga I, Raeber ME, Bowman GR, Novick P, Pande VS, Fathman CG, Boyman O, Garcia KC Nature. 2012 Mar 25. doi: 10.1038/nature10975. PMID:22446627<ref>PMID:22446627</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3qb1" style="background-color:#fffaf0;"></div>~~	+

	==See Also==		==See Also==
	*[[Interleukin 3D structures\|Interleukin 3D structures]]		*[[Interleukin 3D structures\|Interleukin 3D structures]]
-	== References ==
-	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Bates~~, D L~~]]	+	[[Category: Bates DL]]
-	[[Category: Bowman~~, G R~~]]	+	[[Category: Bowman GR]]
-	[[Category: Boyman, O]]	+	[[Category: Boyman O]]
-	[[Category: Fathman~~, C G~~]]	+	[[Category: Fathman CG]]
-	[[Category: Garcia~~, K C~~]]	+	[[Category: Garcia KC]]
-	[[Category: Khort~~, H E~~]]	+	[[Category: Khort HE]]
-	[[Category: Krieg, C]]	+	[[Category: Krieg C]]
-	[[Category: Levin~~, A M~~]]	+	[[Category: Levin AM]]
-	[[Category: Lin~~, J T~~]]	+	[[Category: Lin JT]]
-	[[Category: Novick, P]]	+	[[Category: Novick P]]
-	[[Category: Pande~~, V S~~]]	+	[[Category: Pande VS]]
-	[[Category: Ring~~, A M~~]]	+	[[Category: Ring AM]]
-	[[Category: Su, L]]	+	[[Category: Su L]]
-	~~[[Category: Cytokine]]~~	+
-	~~[[Category: High affinity il-2 cytokine~~]]	+

OCA at 06:00, 8 June 2022

OCA — Wed, 08 Jun 2022 06:00:21 GMT

←Older revision		Revision as of 06:00, 8 June 2022
Line 1:		Line 1:

	==Interleukin-2 mutant D10==		==Interleukin-2 mutant D10==
-	<StructureSection load='3qb1' size='340' side='right' caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>	+	<StructureSection load='3qb1' size='340' side='right'caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qb1]] is a 8 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB1 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3QB1 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qb1]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QB1 FirstGlance]. <br>
-	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qaz\|3qaz]], [[3ink\|3ink]], [[1m47\|1m47]]</td></tr>	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3qaz\|3qaz]], [[3ink\|3ink]], [[1m47\|1m47]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL2 ([~~http~~://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL2 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [~~http~~://pdbe.org/3qb1 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3qb1 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb1 ProSAT]</span></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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [https://pdbe.org/3qb1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [https://www.ebi.ac.uk/pdbsum/3qb1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== 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 ==		== 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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 23:		Line 23:

	==See Also==		==See Also==
-	*[[Interleukin\|Interleukin]]	+	*[[Interleukin 3D structures\|Interleukin 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Bates, D L]]		[[Category: Bates, D L]]
	[[Category: Bowman, G R]]		[[Category: Bowman, G R]]

OCA at 11:42, 11 August 2016

OCA — Thu, 11 Aug 2016 11:42:42 GMT

←Older revision		Revision as of 11:42, 11 August 2016
Line 1:		Line 1:
		+
	==Interleukin-2 mutant D10==		==Interleukin-2 mutant D10==
	<StructureSection load='3qb1' size='340' side='right' caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>		<StructureSection load='3qb1' size='340' side='right' caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>
Line 5:		Line 6:
	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qaz\|3qaz]], [[3ink\|3ink]], [[1m47\|1m47]]</td></tr>		</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qaz\|3qaz]], [[3ink\|3ink]], [[1m47\|1m47]]</td></tr>
	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>		<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [http://www.ebi.ac.uk/pdbsum/3qb1 PDBsum]</span></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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [http://pdbe.org/3qb1 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [http://www.ebi.ac.uk/pdbsum/3qb1 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qb1 ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 19:		Line 20:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3qb1" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==

OCA at 06:39, 22 January 2015

OCA — Thu, 22 Jan 2015 06:39:25 GMT

←Older revision		Revision as of 06:39, 22 January 2015
Line 19:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+
		+	==See Also==
		+	*[[Interleukin\|Interleukin]]
	== References ==		== References ==
	<references/>		<references/>
Line 24:		Line 27:
	</StructureSection>		</StructureSection>
	[[Category: Human]]		[[Category: Human]]
-	[[Category: Bates, D L.]]	+	[[Category: Bates, D L]]
-	[[Category: Bowman, G R.]]	+	[[Category: Bowman, G R]]
-	[[Category: Boyman, O.]]	+	[[Category: Boyman, O]]
-	[[Category: Fathman, C G.]]	+	[[Category: Fathman, C G]]
-	[[Category: Garcia, K C.]]	+	[[Category: Garcia, K C]]
-	[[Category: Khort, H E.]]	+	[[Category: Khort, H E]]
-	[[Category: Krieg, C.]]	+	[[Category: Krieg, C]]
-	[[Category: Levin, A M.]]	+	[[Category: Levin, A M]]
-	[[Category: Lin, J T.]]	+	[[Category: Lin, J T]]
-	[[Category: Novick, P.]]	+	[[Category: Novick, P]]
-	[[Category: Pande, V S.]]	+	[[Category: Pande, V S]]
-	[[Category: Ring, A M.]]	+	[[Category: Ring, A M]]
-	[[Category: Su, L.]]	+	[[Category: Su, L]]
	[[Category: Cytokine]]		[[Category: Cytokine]]
	[[Category: High affinity il-2 cytokine]]		[[Category: High affinity il-2 cytokine]]

OCA at 08:29, 20 October 2014

OCA — Mon, 20 Oct 2014 08:29:21 GMT

←Older revision		Revision as of 08:29, 20 October 2014
Line 1:		Line 1:
-	~~{{STRUCTURE_3qb1\| PDB~~=3qb1 \| ~~SCENE~~= }}	+	==Interleukin-2 mutant D10==
-	===~~Interleukin-~~2 ~~mutant D10~~===	+	<StructureSection load='3qb1' size='340' side='right' caption='[[3qb1]], [[Resolution\|resolution]] 3.10Å' scene=''>
-	~~{{ABSTRACT_PUBMED_22446627}}~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[3qb1]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QB1 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QB1 FirstGlance]. <br>
-	==Disease==	+	</td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3qaz\|3qaz]], [[3ink\|3ink]], [[1m47\|1m47]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">IL2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=3qb1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qb1 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qb1 RCSB], [http://www.ebi.ac.uk/pdbsum/3qb1 PDBsum]</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.		[[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 ==
-	==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.		[[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 ==
		+	The immunostimulatory cytokine interleukin-2 (IL-2) is a growth factor for a wide range of leukocytes, including T cells and natural killer (NK) cells. Considerable effort has been invested in using IL-2 as a therapeutic agent for a variety of immune disorders ranging from AIDS to cancer. However, adverse effects have limited its use in the clinic. On activated T cells, IL-2 signals through a quaternary 'high affinity' receptor complex consisting of IL-2, IL-2Ralpha (termed CD25), IL-2Rbeta and IL-2Rgamma. Naive T cells express only a low density of IL-2Rbeta and IL-2Rgamma, and are therefore relatively insensitive to IL-2, but acquire sensitivity after CD25 expression, which captures the cytokine and presents it to IL-2Rbeta and IL-2Rgamma. Here, using in vitro evolution, we eliminated the functional requirement of IL-2 for CD25 expression by engineering an IL-2 'superkine' (also called super-2) with increased binding affinity for IL-2Rbeta. Crystal structures of the IL-2 superkine in free and receptor-bound forms showed that the evolved mutations are principally in the core of the cytokine, and molecular dynamics simulations indicated that the evolved mutations stabilized IL-2, reducing the flexibility of a helix in the IL-2Rbeta binding site, into an optimized receptor-binding conformation resembling that when bound to CD25. The evolved mutations in the IL-2 superkine recapitulated the functional role of CD25 by eliciting potent phosphorylation of STAT5 and vigorous proliferation of T cells irrespective of CD25 expression. Compared to IL-2, the IL-2 superkine induced superior expansion of cytotoxic T cells, leading to improved antitumour responses in vivo, and elicited proportionally less expansion of T regulatory cells and reduced pulmonary oedema. Collectively, we show that in vitro evolution has mimicked the functional role of CD25 in enhancing IL-2 potency and regulating target cell specificity, which has implications for immunotherapy.

-	~~==About this Structure==~~	+	Exploiting a natural conformational switch to engineer an interleukin-2 'superkine',Levin AM, Bates DL, Ring AM, Krieg C, Lin JT, Su L, Moraga I, Raeber ME, Bowman GR, Novick P, Pande VS, Fathman CG, Boyman O, Garcia KC Nature. 2012 Mar 25. doi: 10.1038/nature10975. PMID:22446627<ref>PMID:22446627</ref>
-	~~[[3qb1]] is~~ a ~~8 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=3QB1 OCA].~~	+
-		+
-	~~==See Also==~~	+
-	*[[Interleukin\|Interleukin]]	+

-	==~~Reference~~==	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	~~<ref group="xtra">PMID:022446627</ref>~~<references ~~group="xtra"~~/><~~references~~/>	+	</div>
-	[[Category: ~~Homo sapiens~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Human]]
	[[Category: Bates, D L.]]		[[Category: Bates, D L.]]
	[[Category: Bowman, G R.]]		[[Category: Bowman, G R.]]
	[[Category: Boyman, O.]]		[[Category: Boyman, O.]]
-	[[Category: C G~~., Fathman~~.]]	+	[[Category: Fathman, C G.]]
	[[Category: Garcia, K C.]]		[[Category: Garcia, K C.]]
	[[Category: Khort, H E.]]		[[Category: Khort, H E.]]

OCA at 19:34, 24 March 2013

OCA — Sun, 24 Mar 2013 19:34:40 GMT

←Older revision		Revision as of 19:34, 24 March 2013
Line 1:		Line 1:
-	[[Image:3qb1.png\|left\|200px]]
-
-	<!--
-	The line below this paragraph, containing "STRUCTURE_3qb1", creates the "Structure Box" on the page.
-	You may change the PDB parameter (which sets the PDB file loaded into the applet)
-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-	or leave the SCENE parameter empty for the default display.
-	-->
	{{STRUCTURE_3qb1\| PDB=3qb1 \| SCENE= }}		{{STRUCTURE_3qb1\| PDB=3qb1 \| SCENE= }}
-
	===Interleukin-2 mutant D10===		===Interleukin-2 mutant D10===
		+	{{ABSTRACT_PUBMED_22446627}}

		+	==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==
-	~~The line below this paragraph, {{ABSTRACT_PUBMED_22446627}}, adds the Publication Abstract to the page~~	+	[[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.
-	~~(as it appears on PubMed at~~ http://www.~~pubmed~~.~~gov)~~, ~~where 22446627~~ is the ~~PubMed ID number~~.	+
-	-->	+
-	~~{{ABSTRACT_PUBMED_22446627}}~~	+

	==About this Structure==		==About this Structure==
	[[3qb1]] is a 8 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=3QB1 OCA].		[[3qb1]] is a 8 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=3QB1 OCA].
		+
		+	==See Also==
		+	*[[Interleukin\|Interleukin]]

	==Reference==		==Reference==
-	<ref group="xtra">PMID:022446627</ref><references group="xtra"/>	+	<ref group="xtra">PMID:022446627</ref><references group="xtra"/><references/>
	[[Category: Homo sapiens]]		[[Category: Homo sapiens]]
	[[Category: Bates, D L.]]		[[Category: Bates, D L.]]

OCA at 18:16, 2 May 2012

OCA — Wed, 02 May 2012 18:16:20 GMT

←Older revision		Revision as of 18:16, 2 May 2012
Line 1:		Line 1:
-	[[Image:3qb1.~~jpg~~\|left\|200px]]	+	[[Image:3qb1.png\|left\|200px]]

	<!--		<!--

OCA at 07:02, 11 April 2012

OCA — Wed, 11 Apr 2012 07:02:06 GMT

←Older revision		Revision as of 07:02, 11 April 2012
Line 1:		Line 1:
-	~~'''Unreleased structure'''~~	+	[[Image:3qb1.jpg\|left\|200px]]

-	The ~~entry 3qb1~~ is ~~ON HOLD~~ ~~until Jun 10 2013~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3qb1", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3qb1\| PDB=3qb1 \| SCENE= }}

-	~~Authors: Levin, A.M., Bates, D.L., Ring, A.M., Lin, J.T., Su, L., Krieg, C., Bowman, G.R., Novick, P., Pande, V.S., Khort, H.E., Boyman, O., Fathman C.G., Garcia, K.C.~~	+	===Interleukin-2 mutant D10===

-	~~Description~~: ~~Interleukin~~-2 ~~mutant D10~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_22446627}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 22446627 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_22446627}}
		+
		+	==About this Structure==
		+	[[3qb1]] is a 8 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=3QB1 OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:022446627</ref><references group="xtra"/>
		+	[[Category: Homo sapiens]]
		+	[[Category: Bates, D L.]]
		+	[[Category: Bowman, G R.]]
		+	[[Category: Boyman, O.]]
		+	[[Category: C G., Fathman.]]
		+	[[Category: Garcia, K C.]]
		+	[[Category: Khort, H E.]]
		+	[[Category: Krieg, C.]]
		+	[[Category: Levin, A M.]]
		+	[[Category: Lin, J T.]]
		+	[[Category: Novick, P.]]
		+	[[Category: Pande, V S.]]
		+	[[Category: Ring, A M.]]
		+	[[Category: Su, L.]]
		+	[[Category: Cytokine]]
		+	[[Category: High affinity il-2 cytokine]]

OCA at 07:13, 22 February 2012

OCA — Wed, 22 Feb 2012 07:13:35 GMT

←Older revision		Revision as of 07:13, 22 February 2012
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3qb1 is ON HOLD until ~~Feb 20~~ 2013	+	The entry 3qb1 is ON HOLD until Jun 10 2013

	Authors: Levin, A.M., Bates, D.L., Ring, A.M., Lin, J.T., Su, L., Krieg, C., Bowman, G.R., Novick, P., Pande, V.S., Khort, H.E., Boyman, O., Fathman C.G., Garcia, K.C.		Authors: Levin, A.M., Bates, D.L., Ring, A.M., Lin, J.T., Su, L., Krieg, C., Bowman, G.R., Novick, P., Pande, V.S., Khort, H.E., Boyman, O., Fathman C.G., Garcia, K.C.

	Description: Interleukin-2 mutant D10		Description: Interleukin-2 mutant D10

OCA at 06:32, 28 December 2011

OCA — Wed, 28 Dec 2011 06:32:52 GMT

←Older revision		Revision as of 06:32, 28 December 2011
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3qb1 is ON HOLD until ~~Paper Publication~~	+	The entry 3qb1 is ON HOLD until Feb 20 2013

	Authors: Levin, A.M., Bates, D.L., Ring, A.M., Lin, J.T., Su, L., Krieg, C., Bowman, G.R., Novick, P., Pande, V.S., Khort, H.E., Boyman, O., Fathman C.G., Garcia, K.C.		Authors: Levin, A.M., Bates, D.L., Ring, A.M., Lin, J.T., Su, L., Krieg, C., Bowman, G.R., Novick, P., Pande, V.S., Khort, H.E., Boyman, O., Fathman C.G., Garcia, K.C.

	Description: Interleukin-2 mutant D10		Description: Interleukin-2 mutant D10