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| | <StructureSection load='7m2g' size='340' side='right'caption='[[7m2g]], [[Resolution|resolution]] 1.79Å' scene=''> | | <StructureSection load='7m2g' size='340' side='right'caption='[[7m2g]], [[Resolution|resolution]] 1.79Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[7m2g]] is a 1 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=7M2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M2G FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7m2g]] is a 1 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=7M2G OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7M2G FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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]] 1.79Å</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=7m2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m2g OCA], [https://pdbe.org/7m2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m2g RCSB], [https://www.ebi.ac.uk/pdbsum/7m2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m2g 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=7m2g FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7m2g OCA], [https://pdbe.org/7m2g PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7m2g RCSB], [https://www.ebi.ac.uk/pdbsum/7m2g PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7m2g 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;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 7m2g" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 7m2g" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Maskos, K]] | + | [[Category: Maskos K]] |
| - | [[Category: Milla, M E]] | + | [[Category: Milla ME]] |
| - | [[Category: Ptacin, J L]] | + | [[Category: Ptacin JL]] |
| - | [[Category: Steinbacher, S]] | + | [[Category: Steinbacher S]] |
| - | [[Category: Thomsen, M]] | + | [[Category: Thomsen M]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Cytokine il-2 mutein human]]
| + | |
| Structural highlights
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
The implementation of applied engineering principles to create synthetic biological systems promises to revolutionize medicine, but application of fundamentally redesigned organisms has thus far not impacted practical drug development. Here we utilize an engineered microbial organism with a six-letter semi-synthetic DNA code to generate a library of site-specific, click chemistry compatible amino acid substitutions in the human cytokine IL-2. Targeted covalent modification of IL-2 variants with PEG polymers and screening identifies compounds with distinct IL-2 receptor specificities and improved pharmacological properties. One variant, termed THOR-707, selectively engages the IL-2 receptor beta/gamma complex without engagement of the IL-2 receptor alpha. In mice, administration of THOR-707 results in large-scale activation and amplification of CD8(+) T cells and NK cells, without Treg expansion characteristic of IL-2. In syngeneic B16-F10 tumor-bearing mice, THOR-707 enhances drug accumulation in the tumor tissue, stimulates tumor-infiltrating CD8(+) T and NK cells, and leads to a dose-dependent reduction of tumor growth. These results support further characterization of the immune modulatory, anti-tumor properties of THOR-707 and represent a fundamental advance in the application of synthetic biology to medicine, leveraging engineered semi-synthetic organisms as cellular factories to facilitate discovery and production of differentiated classes of chemically modified biologics.
An engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism.,Ptacin JL, Caffaro CE, Ma L, San Jose Gall KM, Aerni HR, Acuff NV, Herman RW, Pavlova Y, Pena MJ, Chen DB, Koriazova LK, Shawver LK, Joseph IB, Milla ME Nat Commun. 2021 Aug 9;12(1):4785. doi: 10.1038/s41467-021-24987-9. PMID:34373459[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ptacin JL, Caffaro CE, Ma L, San Jose Gall KM, Aerni HR, Acuff NV, Herman RW, Pavlova Y, Pena MJ, Chen DB, Koriazova LK, Shawver LK, Joseph IB, Milla ME. An engineered IL-2 reprogrammed for anti-tumor therapy using a semi-synthetic organism. Nat Commun. 2021 Aug 9;12(1):4785. doi: 10.1038/s41467-021-24987-9. PMID:34373459 doi:http://dx.doi.org/10.1038/s41467-021-24987-9
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