Download MendeleyStructural and Physical Basis for Anti-IgE Therapy.
Wright, J.D., Chu, H.M., Huang, C.H., Ma, C., Chang, T.W., Lim, C.(2015) Sci Rep 5: 11581-11581
- PubMed: 26113483
- DOI: https://doi.org/10.1038/srep11581
- Primary Citation of Related Structures:
2XA8 - PubMed Abstract:
Omalizumab, an anti-IgE antibody, used to treat severe allergic asthma and chronic idiopathic urticaria, binds to IgE in blood or membrane-bound on B lymphocytes but not to IgE bound to its high (FcεRI) or low (CD23) affinity receptor. Mutagenesis studies indicate overlapping FcεRI and omalizumab-binding sites in the Cε3 domain, but crystallographic studies show FcεRI and CD23-binding sites that are far apart, so how can omalizumab block IgE from binding both receptors? We report a 2.42-Å omalizumab-Fab structure, a docked IgE-Fc/omalizumab-Fab structure consistent with available experimental data, and the free energy contributions of IgE residues to binding omalizumab, CD23, and FcεRI. These results provide a structural and physical basis as to why omalizumab cannot bind receptor-bound IgE and why omalizumab-bound IgE cannot bind to CD23/FcεRI. They reveal the key IgE residues and their roles in binding omalizumab, CD23, and FcεRI.
Organizational Affiliation:
1] Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan [2] The Genomics Research Center, Academia Sinica 115, Taiwan.
