6OY4

Crystal structure of complex between recombinant Der p 2.0103 and Fab fragment of 7A1

Summary for 6OY4

• Entry DOI: 10.2210/pdb6oy4/pdb
• Descriptor: Der p 2 variant 3, Fab fragment of IgG, LIGHT CHAIN, Fab fragment of IgG, HEAVY CHAIN, ... (5 entities in total)
• Functional Keywords: allergen, dust mite, antibody binding, allergen-immune system complex, allergen/immune system
• Biological source: Dermatophagoides pteronyssinus (European house dust mite); More
• Total number of polymer chains: 3
• Total formula weight: 61718.97

Authors

Kapingidza, A.B.,Offermann, L.R.,Glesner, J.,Wunschmann, S.,Vailes, L.D.,Chapman, M.D.C.,Pomes, A.,Chruszcz, M. (deposition date: 2019-05-14, release date: 2019-08-28, Last modification date: 2024-10-16)

Primary citation

Glesner, J.,Kapingidza, A.B.,Godzwon, M.,Offermann, L.R.,Mueller, G.A.,DeRose, E.F.,Wright, P.,Richardson, C.M.,Woodfolk, J.A.,Vailes, L.D.,Wunschmann, S.,London, R.E.,Chapman, M.D.,Ohlin, M.,Chruszcz, M.,Pomes, A.
A Human IgE Antibody Binding Site on Der p 2 for the Design of a Recombinant Allergen for Immunotherapy.
J Immunol., 203:2545-2556, 2019

PubMed Abstract: Der p 2 is one of the most important allergens from the house dust mite Identification of human IgE Ab binding epitopes can be used for rational design of allergens with reduced IgE reactivity for therapy. Antigenic analysis of Der p 2 was performed by site-directed mutagenesis based on the x-ray crystal structure of the allergen in complex with a Fab from the murine IgG mAb 7A1 that binds an epitope overlapping with human IgE binding sites. Conformational changes upon Ab binding were confirmed by nuclear magnetic resonance using a 7A1-single-chain variable fragment. In addition, a human IgE Ab construct that interferes with mAb 7A1 binding was isolated from a combinatorial phage-display library constructed from a mite-allergic patient and expressed as two recombinant forms (single-chain Fab in and Fab in ). These two IgE Ab constructs and the mAb 7A1 failed to recognize two Der p 2 epitope double mutants designed to abolish the allergen-Ab interaction while preserving the fold necessary to bind Abs at other sites of the allergen surface. A 10-100-fold reduction in binding of IgE from allergic subjects to the mutants additionally showed that the residues mutated were involved in IgE Ab binding. In summary, mutagenesis of a Der p 2 epitope defined by x-ray crystallography revealed an IgE Ab binding site that will be considered for the design of hypoallergens for immunotherapy.

PubMed: 31554696
DOI: 10.4049/jimmunol.1900580

Experimental method

X-RAY DIFFRACTION (2.45 Å)