Mapping the Interactions between a Major Pollen Allergen and Human IgE Antibodies

Abstract

The interaction of specific IgE antibodies with allergens is a key event in the induction of allergic symptoms, thus representing an important target for therapeutic interventions in Type I allergies. We report here the solution NMR structure of Art v 1, the major mugwort pollen allergen. Art v 1 is the first protein structure with an allergenic defensin fold linked to a polyproline domain, which has not been identified in any reported allergen structure in the PDB. Moreover, the direct interaction of polyclonal IgE antibodies from an allergic patient has been mapped on the surface of an allergen for the first time. The data presented herein provide the basis for the design of tools for safe and effective vaccination against mugwort pollen allergy.

Phosphorylation-induced Conformational Ensemble Switching in an Intrinsically Disordered Cancer/Testis Antigen

“…Notably, seven of the 11 prolines in PAGE4 have a PX 7 -PX 7 -PPX 7 -PX 7 PP sequence motif from residues 19 -53 that does not occur in the other PAGE family members and likely contributes to these conformational tendencies. A similar sequence motif with disordered extended conformations has been observed in a pollen allergen (54). There are also differences in the helical preferences of PAGE4 and PAGE5.…”

Structure of allergens and structure based epitope predictions

“…Unstructured regions are typically missing in X-ray structures and are characterized by poorly defined NMR structure bundles and differences in their relaxation behavior compared to well-structured parts. Relatively large unstructured regions were found for example in the mugwort pollen allergen Art v 1 [26], the tropical mite allergen Blo t 5 [27] and the olive tree pollen allergen Ole e 6 [28]. In contrast to IgG, IgE binds mainly to structured proteins.…”

Identification of Critical Amino Acids in an Immunodominant IgE Epitope of Pen c 13, a Major Allergen from Penicillium citrinum

“…In a 3D model of Pen c 13 based on the structure of Lecanicillium psalliotae Ver112, the IgE-binding determinant 261 TSSISRAPSGTTSK 274 assumes a loop-like structure on the surface of the protein. This finding is consistent with the known importance of loop-like structures in IgE binding and the reported allergenicity of other allergens, such as transaldolase, a fungal allergen whose IgE-reacting fragment is located in a loop-like structure of the C-terminal region [47]; the dust mite allergen Der f 7, whose IgE-binding epitope forms a loop-like structure on the surface of the protein [48]; the olive pollen allergen Ole e 9, whose B-cell epitopes within the C-terminal domain are mainly located in loops [49]; the mugwort pollen allergen Art v 1, whose non-linear IgE epitopes are found within exposed loop regions harboring lysine residues [50]; and the bovine milk allergen β-lactoglobulin, whose strongest IgE epitope is located in a loop [51]. Furthermore, IgE interactions with hyaluronidase, a major bee venom allergen, may also involve a surface-exposed loop-like IgE determinant [52].…”