Structure of the major peanut allergen Ara h 1 may protect IgE-binding epitopes from degradation

In the past decade, there has been an increase in allergic reactions to pea nut proteins, sometimes resulting in fatal anaphylaxis, The development of improved methods for diagnosis and treatment of peanut allergies requires a better understanding of the structure of the allergens. Ara h 1, a major p eanut allergen belonging to the vicilin family of seed storage proteins, is recognized by serum IgE from >90% of peanut-allergic patients. In this com munication, Are h I was shown to form a highly stable homotrimer. Hydrophob ic interactions were determined to be the main molecular force holding mono mers together. A molecular model of the Ara h 1 trimer was constructed to v iew the stabilizing hydrophobic residues in the three dimensional structure , Hydrophobic amino acids that contribute to trimer formation are at the di stal ends of the three dimensional structure where monomer-monomer contacts occur. Coincidentally, the majority of the IgE-binding epitopes are also l ocated in this region, suggesting that they may be protected from digestion by the monomer-monomer contacts, On incubation of Ara h 1 with digestive e nzymes, various protease-resistant fragments containing IgE-binding sites w ere identified, The highly stable nature of the Ara h 1 trimer, the presenc e of digestion resistant fragments, and the strategic location of the IgE-b inding, epitopes indicate that the quaternary structure of a protein may pl ay a significant role in overall allergenicity.