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| | ==Crystal structure of the complex between IL-13 and M1295 FAB== | | ==Crystal structure of the complex between IL-13 and M1295 FAB== |
| - | <StructureSection load='4ps4' size='340' side='right' caption='[[4ps4]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='4ps4' size='340' side='right'caption='[[4ps4]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4ps4]] is a 3 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3l5y 3l5y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PS4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4ps4]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=3l5y 3l5y]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PS4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PS4 FirstGlance]. <br> |
| - | </td></tr><tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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]] 2.8Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3l5w|3l5w]], [[3l5x|3l5x]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCA:PYROGLUTAMIC+ACID'>PCA</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=4ps4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps4 OCA], [https://pdbe.org/4ps4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ps4 RCSB], [https://www.ebi.ac.uk/pdbsum/4ps4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps4 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=4ps4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ps4 OCA], [http://pdbe.org/4ps4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ps4 RCSB], [http://www.ebi.ac.uk/pdbsum/4ps4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ps4 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. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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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: Gilliland, G L]] | + | [[Category: Large Structures]] |
| - | [[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: 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.
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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