5G64
The complex between human IgE-Fc and two anti-IgE Fab fragments
Summary for 5G64
| Entry DOI | 10.2210/pdb5g64/pdb |
| Descriptor | IG EPSILON CHAIN C REGION, FAB FRAGMENT, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (4 entities in total) |
| Functional Keywords | immune system, immunoglobulin e, omalizumab, ige-fc |
| Biological source | HOMO SAPIENS (HUMAN) More |
| Total number of polymer chains | 6 |
| Total formula weight | 171887.04 |
| Authors | Davies, A.M.,Allan, E.G.,Keeble, A.H.,Delgado, J.,Cossins, B.P.,Mitropoulou, A.N.,Pang, M.O.Y.,Ceska, T.,Beavil, A.J.,Craggs, G.,Westwood, M.,Henry, A.J.,McDonnell, J.M.,Sutton, B.J. (deposition date: 2016-06-14, release date: 2017-05-03, Last modification date: 2024-10-23) |
| Primary citation | Davies, A.M.,Allan, E.G.,Keeble, A.H.,Delgado, J.,Cossins, B.P.,Mitropoulou, A.N.,Pang, M.O.Y.,Ceska, T.,Beavil, A.J.,Craggs, G.,Westwood, M.,Henry, A.J.,McDonnell, J.M.,Sutton, B.J. Allosteric mechanism of action of the therapeutic anti-IgE antibody omalizumab. J. Biol. Chem., 292:9975-9987, 2017 Cited by PubMed Abstract: Immunoglobulin E and its interactions with receptors FcϵRI and CD23 play a central role in allergic disease. Omalizumab, a clinically approved therapeutic antibody, inhibits the interaction between IgE and FcϵRI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and antigen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each Cϵ3 domain. Free IgE-Fc adopts an acutely bent structure, but in the complex it is only partially bent, with large-scale conformational changes in the Cϵ3 domains that inhibit the interaction with FcϵRI. CD23 binding is inhibited sterically due to overlapping binding sites on each Cϵ3 domain. Studies of omalizumab Fab binding in solution demonstrate the allosteric basis for FcϵRI inhibition and, together with the structure, reveal how omalizumab may accelerate dissociation of receptor-bound IgE from FcϵRI, exploiting the intrinsic flexibility and allosteric potential of IgE. PubMed: 28438838DOI: 10.1074/jbc.M117.776476 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.715 Å) |
Structure validation
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