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| - | {{Large structure}}
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| | ==Solution structure of a scFv-IL-1B complex== | | ==Solution structure of a scFv-IL-1B complex== |
| - | <StructureSection load='2kh2' size='340' side='right' caption='[[2kh2]], [[NMR_Ensembles_of_Models | 77 NMR models]]' scene=''> | + | <StructureSection load='2kh2' size='340' side='right'caption='[[2kh2]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2kh2]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KH2 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2KH2 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2kh2]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2KH2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2KH2 FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL1B, IL1F2 ([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">Solution NMR, 77 models</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=2kh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kh2 OCA], [http://pdbe.org/2kh2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2kh2 RCSB], [http://www.ebi.ac.uk/pdbsum/2kh2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2kh2 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=2kh2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2kh2 OCA], [https://pdbe.org/2kh2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2kh2 RCSB], [https://www.ebi.ac.uk/pdbsum/2kh2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2kh2 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| - | {{Large structure}} | |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN]] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref> | + | [https://www.uniprot.org/uniprot/IL1B_HUMAN IL1B_HUMAN] Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.<ref>PMID:3920526</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | <jmolCheckbox> | | <jmolCheckbox> |
| | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kh/2kh2_consurf.spt"</scriptWhenChecked> | | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/kh/2kh2_consurf.spt"</scriptWhenChecked> |
| - | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | + | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
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| | ==See Also== | | ==See Also== |
| | *[[Antibody 3D structures|Antibody 3D structures]] | | *[[Antibody 3D structures|Antibody 3D structures]] |
| - | *[[Interleukin|Interleukin]] | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] |
| | + | *[[3D structures of non-human antibody|3D structures of non-human antibody]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Carr, M D]] | + | [[Category: Mus musculus]] |
| - | [[Category: Hall, C J]] | + | [[Category: Carr MD]] |
| - | [[Category: Henry, A J]] | + | [[Category: Hall CJ]] |
| - | [[Category: Muskett, F W]] | + | [[Category: Henry AJ]] |
| - | [[Category: Stephens, P E]] | + | [[Category: Muskett FW]] |
| - | [[Category: Taylor, R J]] | + | [[Category: Stephens PE]] |
| - | [[Category: Veverka, V]] | + | [[Category: Taylor RJ]] |
| - | [[Category: Wilkinson, I C]] | + | [[Category: Veverka V]] |
| - | [[Category: Antibody]]
| + | [[Category: Wilkinson IC]] |
| - | [[Category: Cytokine]]
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| - | [[Category: Cytokine-immune system complex]]
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| - | [[Category: Il-1b]]
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| - | [[Category: Inflammatory response]]
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| - | [[Category: Mitogen]]
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| - | [[Category: Pyrogen]]
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| - | [[Category: Scfv]]
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| - | [[Category: Secreted]]
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| - | [[Category: Single chain fv]]
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| Structural highlights
Function
IL1B_HUMAN Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Monoclonal antibodies have recently started to deliver on their promise as highly specific and active drugs; however, a more effective, knowledge-based approach to the selection, design, and optimization of potential therapeutic antibodies is currently limited by the surprising lack of detailed structural information for complexes formed with target proteins. Here we show that complexes formed with minimal antigen binding single chain variable fragments (scFv) reliably reflect all the features of the binding interface present in larger Fab fragments, which are commonly used as therapeutics, and report the development of a robust, reliable, and relatively rapid approach to the determination of high resolution models for scFv-target protein complexes. This NMR spectroscopy-based approach combines experimental determination of the interaction surfaces and relative orientations of the scFv and target protein, with NMR restraint-driven, semiflexible docking of the proteins to produce a reliable and highly informative model of the complex. Experience with scFvs and Fabs targeted at a number of secreted regulatory proteins suggests that the approach will be applicable to many therapeutic antibodies targeted at proteins, and its application is illustrated for a potential therapeutic antibody targeted at the cytokine IL-1beta. The detailed structural information that can be obtained by this approach has the potential to have a major impact on the rational design and development of an increasingly important class of biological pharmaceuticals.
High resolution NMR-based model for the structure of a scFv-IL-1beta complex: potential for NMR as a key tool in therapeutic antibody design and development.,Wilkinson IC, Hall CJ, Veverka V, Shi JY, Muskett FW, Stephens PE, Taylor RJ, Henry AJ, Carr MD J Biol Chem. 2009 Nov 13;284(46):31928-35. Epub 2009 Sep 23. PMID:19776018[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Van Damme J, De Ley M, Opdenakker G, Billiau A, De Somer P, Van Beeumen J. Homogeneous interferon-inducing 22K factor is related to endogenous pyrogen and interleukin-1. Nature. 1985 Mar 21-27;314(6008):266-8. PMID:3920526
- ↑ Wilkinson IC, Hall CJ, Veverka V, Shi JY, Muskett FW, Stephens PE, Taylor RJ, Henry AJ, Carr MD. High resolution NMR-based model for the structure of a scFv-IL-1beta complex: potential for NMR as a key tool in therapeutic antibody design and development. J Biol Chem. 2009 Nov 13;284(46):31928-35. Epub 2009 Sep 23. PMID:19776018 doi:M109.025304
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