7sht
From Proteopedia
(Difference between revisions)
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| - | ==== | + | ==Structure of a partially disrupted IgE high affinity receptor complex bound to an omalizumab variant== |
| - | <StructureSection load='7sht' size='340' side='right'caption='[[7sht]]' scene=''> | + | <StructureSection load='7sht' size='340' side='right'caption='[[7sht]], [[Resolution|resolution]] 7.29Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7sht]] is a 7 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=7SHT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7SHT FirstGlance]. <br> |
| - | </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=7sht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sht OCA], [https://pdbe.org/7sht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sht RCSB], [https://www.ebi.ac.uk/pdbsum/7sht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sht ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 7.29Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7sht FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sht OCA], [https://pdbe.org/7sht PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sht RCSB], [https://www.ebi.ac.uk/pdbsum/7sht PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sht ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/FCERA_HUMAN FCERA_HUMAN] Binds to the Fc region of immunoglobulins epsilon. High affinity receptor. Responsible for initiating the allergic response. Binding of allergen to receptor-bound IgE leads to cell activation and the release of mediators (such as histamine) responsible for the manifestations of allergy. The same receptor also induces the secretion of important lymphokines. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Antibody drugs exert therapeutic effects via a range of mechanisms, including competitive inhibition, allosteric modulation, and immune effector mechanisms. Facilitated dissociation is an additional mechanism where antibody-mediated "disruption" of stable high-affinity macromolecular complexes can potentially enhance therapeutic efficacy. However, this mechanism is not well understood or utilized therapeutically. Here, we investigate and engineer the weak disruptive activity of an existing therapeutic antibody, omalizumab, which targets IgE antibodies to block the allergic response. We develop a yeast display approach to select for and engineer antibody disruptive efficiency and generate potent omalizumab variants that dissociate receptor-bound IgE. We determine a low resolution cryo-EM structure of a transient disruption intermediate containing the IgE-Fc, its partially dissociated receptor and an antibody inhibitor. Our results provide a conceptual framework for engineering disruptive inhibitors for other targets, insights into the failure in clinical trials of the previous high affinity omalizumab HAE variant and anti-IgE antibodies that safely and rapidly disarm allergic effector cells. | ||
| + | |||
| + | Directed evolution of and structural insights into antibody-mediated disruption of a stable receptor-ligand complex.,Pennington LF, Gasser P, Kleinboelting S, Zhang C, Skiniotis G, Eggel A, Jardetzky TS Nat Commun. 2021 Dec 3;12(1):7069. doi: 10.1038/s41467-021-27397-z. PMID:34862384<ref>PMID:34862384</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7sht" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Monoclonal Antibodies 3D structures|Monoclonal Antibodies 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Jardetzky TS]] |
| + | [[Category: Pennington LF]] | ||
Current revision
Structure of a partially disrupted IgE high affinity receptor complex bound to an omalizumab variant
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