Structure of the major peanut allergen Ara h 1 may protect IgE-binding epitopes from degradation
Structure of the major peanut allergen Ara h 1 may protect IgE-binding epitopes from degradation
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DOI：
10.4049/jimmunol.164.11.5844
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发表时间：
2000-06-01
影响因子：
4.4
通讯作者：
Bannon, GA
中科院分区：
文献类型：
--
作者：
Maleki, SJ;Kopper, RA;Bannon, GA
在过去的十年中，对花生蛋白的过敏反应有所增加，有时会导致致命的过敏反应，花生过敏的诊断和治疗方法的改进需要更好地了解过敏原的结构。Ara h1是一种主要的花生过敏原，属于种子储存蛋白vicilin家族，在90%的花生过敏患者中被血清IgE识别。在这个通讯中，Are h I被证明形成了一个高度稳定的三聚体。疏水相互作用被确定为使单体结合在一起的主要分子力。构建了Ara h 1三聚体的分子模型来观察其在三维结构中的稳定疏水残基，促进三聚体形成的疏水氨基酸位于三维结构中单体与单体接触发生的远端。巧合的是，大多数的ige结合表位也位于这一区域，这表明它们可能受到单体-单体接触的保护而不被消化。在Ara h 1与消化酶孵育的过程中，发现了各种含有ige结合位点的蛋白酶抗性片段。Ara h 1三聚体的高度稳定性，消化抗性片段的存在，以及ige结合的战略位置。表位表明，蛋白质的四级结构可能在总过敏原中起重要作用。
In the past decade, there has been an increase in allergic reactions to peanut 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 peanut allergen belonging to the vicilin family of seed storage proteins, is recognized by serum IgE from >90% of peanut-allergic patients. In this communication, Are h I was shown to form a highly stable homotrimer. Hydrophobic interactions were determined to be the main molecular force holding monomers together. A molecular model of the Ara h 1 trimer was constructed to view the stabilizing hydrophobic residues in the three dimensional structure, Hydrophobic amino acids that contribute to trimer formation are at the distal ends of the three dimensional structure where monomer-monomer contacts occur. Coincidentally, the majority of the IgE-binding epitopes are also located in this region, suggesting that they may be protected from digestion by the monomer-monomer contacts, On incubation of Ara h 1 with digestive enzymes, various protease-resistant fragments containing IgE-binding sites were identified, The highly stable nature of the Ara h 1 trimer, the presence of digestion resistant fragments, and the strategic location of the IgE-binding, epitopes indicate that the quaternary structure of a protein may play a significant role in overall allergenicity.