8VQF

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

Summary for 8VQF

• Entry DOI: 10.2210/pdb8vqf/pdb
• Descriptor: IgE 1J11 Light chain, IgE 1J11 Heavy chain, Major allergen Can f 1, ... (6 entities in total)
• Functional Keywords: 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/immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 66973.35

Authors

Khatri, K.,Ball, A.,Richardson, C.M.,Smith, S.A.,Champan, M.D.,Pomes, A.,Chruszcz, M. (deposition date: 2024-01-18, release date: 2025-01-22, Last modification date: 2025-09-03)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (3.109 Å)