科研之友
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摘要
Immunoglobulin E and its interactions with receptors Fc is an element of RI and CD23 play a central role in allergic disease. Omalizumab, a clinically approved therapeutic antibody, inhibits the interaction between IgE and Fc is an element of RI, preventing mast cell and basophil activation, and blocks IgE binding to CD23 on B cells and anti-gen-presenting cells. We solved the crystal structure of the complex between an omalizumab-derived Fab and IgE-Fc, with one Fab bound to each C is an element of 3 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 C is an element of 3 domains that inhibit the interaction with Fc is an element of RI. CD23 binding is inhibited sterically due to overlapping binding sites on each C is an element of 3 domain. Studies of omalizumab Fab binding in solution demonstrate the allosteric basis for Fc is an element of RI inhibition and, together with the structure, reveal how omalizumab may accelerate dissociation of receptor-bound IgE from Fc is an element of RI, exploiting the intrinsic flexibility and allosteric potential of IgE.
- 出版日期2017-6-16
