9rtg | pdb_00009rtg
Crystal structure of Ara h 2 immunocomplex with IgE Fab fragment
Structural highlights
FunctionCONG7_ARAHY Weak inhibitor of trypsin.[1] Publication Abstract from PubMedBACKGROUND: Peanut allergy is a serious form of food allergy that can lead to anaphylactic reactions. Research has shown that the Ara h 2 allergen is immunodominant and associated with fatal systemic reactions. METHODS: We determined the crystal structure of recombinant Ara h 2.0201 in a complex with the human-derived PA12P3D08 (D08) IgE Fab fragment at 3.2 A resolution. In addition, native mass spectrometry was used to study interactions of D08 with Ara h 2 and its peptides. RESULTS: The structure revealed that D08 Fab binds to a long loop of Ara h 2.0201, which contains three repeated DPYSPS motifs. The immunocomplex structure illustrated how three copies of D08 Fabs can bind simultaneously to Ara h 2.0201 in close proximity. Native mass spectrometry studies of D08 Fab with Ara h 2.0201 and peptides containing 2-3 motifs demonstrated cross-linking of Ara h 2.0201 in solution and the propensity of D08 Fab to self-associate. Motif peptides from Ara h 2.0201 highlighted the importance of proline hydroxylation for binding affinity. D08 Fab also bound to hydroxyproline-containing peptides from Ara h 1 and 3. CONCLUSIONS: The trivalent binding is effective in forming large allergen-IgE complexes on mast cell or basophil surfaces and contributes to the potency of Ara h 2 in triggering allergic reactions and highlighting its role in anaphylaxis. Proline hydroxylation considerably enhances D08 binding affinity and contributes to cross-reactivity among Ara h 1-3 allergens. Structural Basis for Trivalent Cross-Linking of a Patient-Derived IgE Antibody by the Major Peanut Allergen Ara h 2.0201.,Parkkinen T, Heiniluoto H, Janis J, Takkinen K, Rouvinen J Allergy. 2026 Jun;81(6):2036-2046. doi: 10.1111/all.70258. Epub 2026 Feb 17. PMID:41700105[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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