9NPH

X-ray crystal structure of recombinant Can f 1 in complex with human IgE mAb 1J11 Fab

9NPH の概要

• エントリーDOI: 10.2210/pdb9nph/pdb
• 関連するPDBエントリー: 8VQF 8VQG
• 分子名称: 1J11 Fab light chain, 1J11 Fab heavy chain, Major allergen Can f 1, ... (7 entities in total)
• 機能のキーワード: allergen-antibody complex, dog allergen can f 1, anti can f 1 antibody, human ige bound to can f 1, allergen-immune system complex, allergen, allergen/immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 66553.89

構造登録者

Khatri, K.,Ball, A.,Smith, S.A.,Champan, M.D.,Pomes, A.,Chruszcz, M. (登録日: 2025-03-11, 公開日: 2025-08-27)

主引用文献

Khatri, K.,Ball, A.,Glesner, J.,Linn, C.,Vailes, L.D.,Wunschmann, S.,Gabel, S.A.,Zhang, J.,Peebles Jr., R.S.,Borowski, T.,Mueller, G.A.,Chapman, M.D.,Smith, S.A.,Pomes, A.,Chruszcz, M.
Human IgE monoclonal antibodies define two unusual epitopes trapping dog allergen Can f 1 in different conformations.
Protein Sci., 34:e70269-e70269, 2025

PubMed Abstract: Molecular analysis of interactions between IgE antibody and allergen allows the structural basis of IgE recognition to be defined. Human IgE (hIgE) epitopes of respiratory lipocalin allergens, including Can f 1, remain elusive due to a lack of IgE-allergen complexes. This study aims to map the structure of allergenic epitopes on Can f 1. The fragment antigen-binding (Fab) regions of Can f 1 specific human IgE monoclonal antibodies (hIgE mAb) were used to determine the structures of IgE epitopes. Epitope mutants were designed to target Can f 1 epitopes. Immunoassays and a human FcεRIα transgenic mouse model of passive anaphylaxis in vivo were used to assess the functional activity of epitope mutants. Crystal structures of natural or recombinant Can f 1 complexed with two hIgE mAb 1J11 and 12F3 Fabs, respectively, were determined. The hIgE mAb bound to two partially overlapping epitopes and recognized two different Can f 1 conformations. The hIgE mAb 12F3 showed an unusual mode of binding by protruding its heavy chain CDR3 inside the Can f 1 calyx. Epitope mutants generated based on the structural analyses displayed a 64%-89% reduction in IgE antibody binding and failed to induce passive anaphylaxis in a human FcεRIα transgenic mouse model. In summary, the structures of Can f 1-hIgE Fab complexes revealed two unique and partially overlapping epitopes on Can f 1. The modification of the identified IgE epitopes provides a pathway for the design of hypoallergens to treat dog allergies.

PubMed: 40828364
DOI: 10.1002/pro.70269

実験手法

X-RAY DIFFRACTION (2.592 Å)