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7ra9
From Proteopedia
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==Designed StabIL-2 seq1== | ==Designed StabIL-2 seq1== | ||
| - | <StructureSection load='7ra9' size='340' side='right'caption='[[7ra9]]' scene=''> | + | <StructureSection load='7ra9' size='340' side='right'caption='[[7ra9]], [[Resolution|resolution]] 2.20Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7RA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RA9 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7ra9]] 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=7RA9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7RA9 FirstGlance]. <br> |
| - | </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=7ra9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ra9 OCA], [https://pdbe.org/7ra9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ra9 RCSB], [https://www.ebi.ac.uk/pdbsum/7ra9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ra9 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]] 2.2Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</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=7ra9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7ra9 OCA], [https://pdbe.org/7ra9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7ra9 RCSB], [https://www.ebi.ac.uk/pdbsum/7ra9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7ra9 ProSAT]</span></td></tr> | ||
</table> | </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. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Affinity maturation of protein-protein interactions is an important approach in the development of therapeutic proteins such as cytokines. Typical experimental strategies involve targeting the cytokine-receptor interface with combinatorial libraries and then selecting for higher-affinity variants. Mutations to the binding scaffold are usually not considered main drivers for improved affinity. Here we demonstrate that computational design can provide affinity-enhanced variants of interleukin-2 (IL-2) "out of the box" without any requirement for interface engineering. Using a strategy of global IL-2 structural stabilization targeting metastable regions of the three-dimensional structure, rather than the receptor binding interfaces, we computationally designed thermostable IL-2 variants with up to 40-fold higher affinity for IL-2Rbeta without any library-based optimization. These IL-2 analogs exhibited CD25-independent activities on T and natural killer (NK) cells both in vitro and in vivo, mimicking the properties of the IL-2 superkine "super-2" that was engineered through yeast surface display [A. M. Levin et al., Nature, 484, 529-533 (2012)]. Structure-guided stabilization of cytokines is a powerful approach to affinity maturation with applications to many cytokine and protein-protein interactions. | ||
| + | |||
| + | Interleukin-2 superkines by computational design.,Ren J, Chu AE, Jude KM, Picton LK, Kare AJ, Su L, Montano Romero A, Huang PS, Garcia KC Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2117401119. doi: , 10.1073/pnas.2117401119. Epub 2022 Mar 16. PMID:35294290<ref>PMID:35294290</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7ra9" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Interleukin 3D structures|Interleukin 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chu AE]] | [[Category: Chu AE]] | ||
Current revision
Designed StabIL-2 seq1
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