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| | ==Computationally designed functional antibody== | | ==Computationally designed functional antibody== |
| - | <StructureSection load='5n7w' size='340' side='right' caption='[[5n7w]], [[Resolution|resolution]] 1.96Å' scene=''> | + | <StructureSection load='5n7w' size='340' side='right'caption='[[5n7w]], [[Resolution|resolution]] 1.96Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5n7w]] is a 6 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=5N7W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5N7W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5n7w]] is a 6 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=5N7W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5N7W FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL17A, CTLA8, IL17 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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]] 1.96Å</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=5n7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n7w OCA], [http://pdbe.org/5n7w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5n7w RCSB], [http://www.ebi.ac.uk/pdbsum/5n7w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5n7w 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=5n7w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5n7w OCA], [https://pdbe.org/5n7w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5n7w RCSB], [https://www.ebi.ac.uk/pdbsum/5n7w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5n7w ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN]] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. | + | [https://www.uniprot.org/uniprot/IL17_HUMAN IL17_HUMAN] Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Breed, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Hargreaves, D]] | + | [[Category: Breed J]] |
| - | [[Category: Computationally designed antibody il17]] | + | [[Category: Hargreaves D]] |
| - | [[Category: Immune system]]
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| Structural highlights
Function
IL17_HUMAN Induces stromal cells to produce proinflammatory and hematopoietic cytokines. Enhances the surface expression of ICAM1/intracellular adhesion molecule 1 in fibroblasts.
Publication Abstract from PubMed
The ultimate goal of protein design is to introduce new biological activity. We propose a computational approach for designing functional antibodies by focusing on functional epitopes, integrating large-scale statistical analysis with multiple structural models. Machine learning is used to analyze these models and predict specific residue-residue contacts. We use this approach to design a functional antibody to counter the proinflammatory effect of the cytokine interleukin-17A (IL-17A). X-ray crystallography confirms that the designed antibody binds the targeted epitope and the interaction is mediated by the designed contacts. Cell-based assays confirm that the antibody is functional. Importantly, this approach does not rely on a high-quality 3D model of the designed complex or even a solved structure of the target. As demonstrated here, this approach can be used to design biologically active antibodies, removing some of the main hurdles in antibody design and in drug discovery.
Computational Design of Epitope-Specific Functional Antibodies.,Nimrod G, Fischman S, Austin M, Herman A, Keyes F, Leiderman O, Hargreaves D, Strajbl M, Breed J, Klompus S, Minton K, Spooner J, Buchanan A, Vaughan TJ, Ofran Y Cell Rep. 2018 Nov 20;25(8):2121-2131.e5. doi: 10.1016/j.celrep.2018.10.081. PMID:30463010[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Nimrod G, Fischman S, Austin M, Herman A, Keyes F, Leiderman O, Hargreaves D, Strajbl M, Breed J, Klompus S, Minton K, Spooner J, Buchanan A, Vaughan TJ, Ofran Y. Computational Design of Epitope-Specific Functional Antibodies. Cell Rep. 2018 Nov 20;25(8):2121-2131.e5. doi: 10.1016/j.celrep.2018.10.081. PMID:30463010 doi:http://dx.doi.org/10.1016/j.celrep.2018.10.081
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