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| | ==Lebrikizumab Fab bound to IL-13== | | ==Lebrikizumab Fab bound to IL-13== |
| - | <StructureSection load='4i77' size='340' side='right' caption='[[4i77]], [[Resolution|resolution]] 1.90Å' scene=''> | + | <StructureSection load='4i77' size='340' side='right'caption='[[4i77]], [[Resolution|resolution]] 1.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4i77]] is a 3 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=4I77 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4I77 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4i77]] is a 3 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=4I77 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4I77 FirstGlance]. <br> |
| - | </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> | + | </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=4i77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i77 OCA], [https://pdbe.org/4i77 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4i77 RCSB], [https://www.ebi.ac.uk/pdbsum/4i77 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4i77 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=4i77 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4i77 OCA], [http://pdbe.org/4i77 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4i77 RCSB], [http://www.ebi.ac.uk/pdbsum/4i77 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4i77 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: Eigenbrot, C]] | + | [[Category: Large Structures]] |
| - | [[Category: Ultsch, M]] | + | [[Category: Eigenbrot C]] |
| - | [[Category: Immune system recognition]] | + | [[Category: Ultsch M]] |
| - | [[Category: Immune system-cytokine complex]]
| + | |
| - | [[Category: Immunoglobulin]]
| + | |
| 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
The cytokine interleukin 13 (IL-13) is a major effector molecule for T-helper type 2 inflammation and is pathogenic in allergic diseases such as asthma. The effects of IL-13 are mediated via a pathway that is initiated by binding to a heterodimeric receptor consisting of IL-13Ralpha1 and IL-4Ralpha. Antibodies raised against IL-13 can block its inflammatory effects by interfering with binding to either of the two receptor polypeptides. Lebrikizumab is a monoclonal anti-IL-13 antibody that has shown clinical benefit in a phase II study for the treatment of moderate-to-severe uncontrolled asthma. Here we report the molecular structure of IL-13 in complex with the Fab from Lebrikizumab by X-ray crystallography at 1.9A resolution. We show that Lebrikizumab inhibits IL-13 signaling by binding to IL-13 with very high affinity and blocking IL-13 binding to IL-4Ralpha. In addition, we use site-directed mutations to identify the most important antibody contributors to binding. Our studies define key features of Lebrikizumab binding and its mechanism of action that may contribute to its clinical effects.
Structural Basis of Signaling Blockade by Anti-IL-13 Antibody Lebrikizumab.,Ultsch M, Bevers J, Nakamura G, Vandlen R, Kelley RF, Wu LC, Eigenbrot C J Mol Biol. 2013 Jan 25. pii: S0022-2836(13)00040-5. doi:, 10.1016/j.jmb.2013.01.024. PMID:23357170[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Ultsch M, Bevers J, Nakamura G, Vandlen R, Kelley RF, Wu LC, Eigenbrot C. Structural Basis of Signaling Blockade by Anti-IL-13 Antibody Lebrikizumab. J Mol Biol. 2013 Jan 25. pii: S0022-2836(13)00040-5. doi:, 10.1016/j.jmb.2013.01.024. PMID:23357170 doi:http://dx.doi.org/10.1016/j.jmb.2013.01.024
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