5NQW

IgE-Fc in complex with single domain antibody 026

5NQW の概要

• エントリーDOI: 10.2210/pdb5nqw/pdb
• 分子名称: Immunoglobulin heavy constant epsilon, 026, alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)-[alpha-D-mannopyranose-(1-3)]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: ige-fc, nanobody, vhh, allergy, immune system
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 79828.77

構造登録者

Laursen, N.S.,Jabs, F.,Spillner, E.,Andersen, G.R. (登録日: 2017-04-21, 公開日: 2018-01-17, 最終更新日: 2024-10-23)

主引用文献

Jabs, F.,Plum, M.,Laursen, N.S.,Jensen, R.K.,Molgaard, B.,Miehe, M.,Mandolesi, M.,Rauber, M.M.,Pfutzner, W.,Jakob, T.,Mobs, C.,Andersen, G.R.,Spillner, E.
Trapping IgE in a closed conformation by mimicking CD23 binding prevents and disrupts Fc epsilon RI interaction.
Nat Commun, 9:7-7, 2018

PubMed Abstract: Anti-IgE therapeutics interfere with the ability of IgE to bind to its receptors on effector cells. Here we report the crystal structure of an anti-IgE single-domain antibody in complex with an IgE Fc fragment, revealing how the antibody inhibits interactions between IgE and the two receptors FcεRI and CD23. The epitope overlaps only slightly with the FcεRI-binding site but significantly with the CD23-binding site. Solution scattering studies of the IgE Fc reveal that antibody binding induces a half-bent conformation in between the well-known bent and extended IgE Fc conformations. The antibody acts as functional homolog of CD23 and induces a closed conformation of IgE Fc incompatible with FcεRI binding. Notably the antibody displaces IgE from both CD23 and FcεRI, and abrogates allergen-mediated basophil activation and facilitated allergen binding. The inhibitory mechanism might facilitate strategies for the future development of anti-IgE therapeutics for treatment of allergic diseases.

PubMed: 29295972
DOI: 10.1038/s41467-017-02312-7

実験手法

X-RAY DIFFRACTION (3.4 Å)