Wurzburg B A, Garman S C, Jardetzky T S
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, Illinois 60208, USA.
Immunity. 2000 Sep;13(3):375-85. doi: 10.1016/s1074-7613(00)00037-6.
IgE antibodies mediate antiparasitic immune responses and the inflammatory reactions of allergy and asthma. We have solved the crystal structure of the human IgE-Fc Cepsilon3-Cepsilon4 domains to 2.3 A resolution. The structure reveals a large rearrangement of the N-terminal Cepsilon3 domains when compared to related IgG-Fc structures and to the IgE-Fc bound to its high-affinity receptor, FcepsilonRI. The IgE-Fc adopts a more compact, closed configuration that places the two Cepsilon3 domains in close proximity, decreases the size of the interdomain cavity, and obscures part of the FcepsilonRI binding site. IgE-Fc conformational flexibility may be required for interactions with two distinct IgE receptors, and the structure suggests strategies for the design of therapeutic compounds for the treatment of IgE-mediated diseases.
IgE抗体介导抗寄生虫免疫反应以及过敏和哮喘的炎症反应。我们已将人IgE-Fc的Cε3-Cε4结构域的晶体结构解析到2.3埃的分辨率。与相关的IgG-Fc结构以及与其高亲和力受体FcepsilonRI结合的IgE-Fc相比，该结构揭示了N端Cε3结构域的大量重排。IgE-Fc采用了更紧凑、封闭的构象，使两个Cε3结构域紧密相邻，减小了结构域间腔的大小，并掩盖了FcepsilonRI结合位点的一部分。IgE-Fc的构象灵活性可能是与两种不同的IgE受体相互作用所必需的，并且该结构为治疗IgE介导疾病的治疗化合物设计提供了策略。
