5G64

The complex between human IgE-Fc and two anti-IgE Fab fragments

5G64 の概要

• エントリーDOI: 10.2210/pdb5g64/pdb
• 分子名称: 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)
• 機能のキーワード: immune system, immunoglobulin e, omalizumab, ige-fc
• 由来する生物種: HOMO SAPIENS (HUMAN); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 171887.04

構造登録者

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. (登録日: 2016-06-14, 公開日: 2017-05-03, 最終更新日: 2024-10-23)

主引用文献

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

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: 28438838
DOI: 10.1074/jbc.M117.776476

実験手法

X-RAY DIFFRACTION (3.715 Å)