Basis of the Intrinsic Flexibility of the Cε3 Domain of IgE
Basis of the Intrinsic Flexibility of the Cε3 Domain of IgE
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DOI：
10.1021/bi200019y
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发表时间：
2011-05-31
期刊：
影响因子：
2.9
通讯作者：
McDonnell, James M.
中科院分区：
文献类型：
--
作者：
Borthakur, Susmita;Andrejeva, Gabriela;McDonnell, James M.
过敏反应是由IgE与其高亲和受体Fc epsilon RI相互作用引发的。各种研究已经将IgE与其细胞受体之间的相互作用表面映射到IgE的第三个恒定结构域（C epsilon 3）。分离的C - epsilon - 3结构域已被证明以熔融球状体的形式存在，并且该结构域在IgE蛋白的环境中保持了显著的灵活性。在此，我们分析了这一领域内在灵活性的结构基础。我们将C - epsilon 3结构域的序列与免疫球蛋白超家族Cl亚群的其他成员的序列进行了比较，观察到C - epsilon 3具有异常高的静电电荷和异常低的疏水残基含量。将C - epsilon 3恢复到更规范的序列的突变被引入，试图获得一个更结构化的结构域，并且一些突变显示出较低的紊乱水平。具有一系列结构刚度的C - epsilon 3工程结构域可以作为阐明C - epsilon 3结构域的灵活性在IgE生物学功能中的作用的重要工具。
Allergic reactions are triggered by the interaction between IgE and its high-affinity receptor, Fc epsilon RI. Various studies have mapped the interaction surface between IgE and its cellular receptors to the third constant domain of IgE (C epsilon 3). The isolated C epsilon 3 domain has been shown to exist as a molten globule, and the domain retains significant flexibility within the context of the IgE protein. Here we have analyzed the structural basis of the intrinsic flexibility of this domain. We have compared the sequence of the C epsilon 3 domain to the sequences of other members of the Cl subset of the immunoglobulin superfamily and observed that C epsilon 3 has an unusually high electrostatic charge and an unusually low content of hydrophobic residues. Mutations restoring C epsilon 3 to a more canonical sequence were introduced in an attempt to derive a more structured domain, and several mutants display decreased levels of disorder. Engineered domains of C epsilon 3 with a range of structural rigidities could serve as important tools for the elucidation of the role of flexibility of the C epsilon 3 domain in IgE's biological functions.