6UQR

Complex of IgE and Ligelizumab

Summary for 6UQR

• Entry DOI: 10.2210/pdb6uqr/pdb
• Descriptor: Ligelizumab, IgE, 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: anti-ige antibody, complex, monoclonal, immune system
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 114692.55

Authors

Tarchevskaya, S.S.,Kleinboelting, S.,Jardetzky, T.S. (deposition date: 2019-10-21, release date: 2019-12-04, Last modification date: 2024-10-30)

Primary citation

Gasser, P.,Tarchevskaya, S.S.,Guntern, P.,Brigger, D.,Ruppli, R.,Zbaren, N.,Kleinboelting, S.,Heusser, C.,Jardetzky, T.S.,Eggel, A.
The mechanistic and functional profile of the therapeutic anti-IgE antibody ligelizumab differs from omalizumab.
Nat Commun, 11:165-165, 2020

PubMed Abstract: Targeting of immunoglobulin E (IgE) represents an interesting approach for the treatment of allergic disorders. A high-affinity monoclonal anti-IgE antibody, ligelizumab, has recently been developed to overcome some of the limitations associated with the clinical use of the therapeutic anti-IgE antibody, omalizumab. Here, we determine the molecular binding profile and functional modes-of-action of ligelizumab. We solve the crystal structure of ligelizumab bound to IgE, and report epitope differences between ligelizumab and omalizumab that contribute to their qualitatively distinct IgE-receptor inhibition profiles. While ligelizumab shows superior inhibition of IgE binding to FcεRI, basophil activation, IgE production by B cells and passive systemic anaphylaxis in an in vivo mouse model, ligelizumab is less potent in inhibiting IgE:CD23 interactions than omalizumab. Our data thus provide a structural and mechanistic foundation for understanding the efficient suppression of FcεRI-dependent allergic reactions by ligelizumab in vitro as well as in vivo.

PubMed: 31913280
DOI: 10.1038/s41467-019-13815-w

Experimental method

X-RAY DIFFRACTION (3.65029109708 Å)