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| | ==Crystal structure of the complex between IL-13 and C836 FAB== | | ==Crystal structure of the complex between IL-13 and C836 FAB== |
| - | <StructureSection load='3l5w' size='340' side='right' caption='[[3l5w]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='3l5w' size='340' side='right'caption='[[3l5w]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3l5w]] is a 6 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 crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L5W OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3L5W FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3l5w]] is a 6 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 crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3L5W OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3L5W FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l5x|3l5x]], [[3l5y|3l5y]]</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></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">IL13, NC30 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3l5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l5w OCA], [https://pdbe.org/3l5w PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3l5w RCSB], [https://www.ebi.ac.uk/pdbsum/3l5w PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3l5w ProSAT]</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=3l5w FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3l5w OCA], [http://pdbe.org/3l5w PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3l5w RCSB], [http://www.ebi.ac.uk/pdbsum/3l5w PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3l5w ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN]] Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:[http://omim.org/entry/607154 607154]]. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure. | + | [https://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN] Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:[https://omim.org/entry/607154 607154]. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN]] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses. | + | [https://www.uniprot.org/uniprot/IL13_HUMAN IL13_HUMAN] Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | ==See Also== | | ==See Also== |
| - | *[[Interleukin|Interleukin]] | + | *[[Interleukin 3D structures|Interleukin 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Gilliland, G L]] | + | [[Category: Mus musculus]] |
| - | [[Category: Malia, T]] | + | [[Category: Gilliland GL]] |
| - | [[Category: Obmolova, G]] | + | [[Category: Malia T]] |
| - | [[Category: Teplyakov, A]] | + | [[Category: Obmolova G]] |
| - | [[Category: Alpha-helical bundle]]
| + | [[Category: Teplyakov A]] |
| - | [[Category: Cytokine]]
| + | |
| - | [[Category: Disulfide bond]]
| + | |
| - | [[Category: Glycoprotein]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Immunoglobulin fold]]
| + | |
| - | [[Category: Monoclonal antibody]]
| + | |
| - | [[Category: Polymorphism]]
| + | |
| - | [[Category: Secreted]]
| + | |
| Structural highlights
Disease
IL13_HUMAN Defects in IL13 may be a cause of susceptibility to allergic rhinitis (ALRH) [MIM:607154. Allergic rhinitis is a common disease of complex inheritance and is characterized by mucosal inflammation caused by allergen exposure.
Function
IL13_HUMAN Cytokine. Inhibits inflammatory cytokine production. Synergizes with IL2 in regulating interferon-gamma synthesis. May be critical in regulating inflammatory and immune responses.
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
Humanization of a potent neutralizing mouse anti-human IL-13 antibody (m836) using a method called human framework adaptation (HFA) is reported. HFA consists of two steps: human framework selection (HFS) and specificity-determining residue optimization (SDRO). The HFS step involved generation of a library of m836 antigen binding sites combined with diverse human germline framework regions (FRs), which were selected based on structural and sequence similarities between mouse variable domains and a repertoire of human antibody germline genes. SDRO consisted of diversifying specificity-determining residues and selecting variants with improved affinity using phage display. HFS of m836 resulted in a 5-fold loss of affinity, whereas SDRO increased the affinity up to 100-fold compared to the HFS antibody. Crystal structures of Fabs in complex with IL-13 were obtained for m836, the HFS variant chosen for SDRO, and one of the highest-affinity SDRO variants. Analysis of the structures revealed that major conformational changes in FR-H1 and FR-H3 occurred after FR replacement, but none of them had an evident direct impact on residues in contact with IL-13. Instead, subtle changes affected the V(L)/V(H) (variable-light domain/variable-heavy domain) interface and were likely responsible for the 5-fold decreased affinity. After SDRO, increased affinity resulted mainly from rearrangements in hydrogen-bonding pattern at the antibody/antigen interface. Comparison with m836 putative germline genes suggested interesting analogies between natural affinity maturation and the engineering process that led to the potent HFA anti-human IL-13 antibody.
Human framework adaptation of a mouse anti-human IL-13 antibody.,Fransson J, Teplyakov A, Raghunathan G, Chi E, Cordier W, Dinh T, Feng Y, Giles-Komar J, Gilliland G, Lollo B, Malia TJ, Nishioka W, Obmolova G, Zhao S, Zhao Y, Swanson RV, Almagro JC J Mol Biol. 2010 Apr 30;398(2):214-31. Epub 2010 Mar 10. PMID:20226193[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Fransson J, Teplyakov A, Raghunathan G, Chi E, Cordier W, Dinh T, Feng Y, Giles-Komar J, Gilliland G, Lollo B, Malia TJ, Nishioka W, Obmolova G, Zhao S, Zhao Y, Swanson RV, Almagro JC. Human framework adaptation of a mouse anti-human IL-13 antibody. J Mol Biol. 2010 Apr 30;398(2):214-31. Epub 2010 Mar 10. PMID:20226193 doi:10.1016/j.jmb.2010.03.004
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