Bivalent binding of IgA1 to FcαRI suggests a mechanism for cytokine activation of IgA phagocytosis
Bivalent binding of IgA1 to FcαRI suggests a mechanism for cytokine activation of IgA phagocytosis
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DOI：
10.1016/s0022-2836(03)00149-9
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发表时间：
2003-03-28
影响因子：
5.6
通讯作者：
Bjorkman, PJ
中科院分区：
文献类型：
--
作者：
Herr, AB;White, CL;Bjorkman, PJ
FcalphaRI 是免疫球蛋白 A (IgA) Fc 区的特异性受体，负责 IgA 介导的吞噬作用、氧化爆发和抗体依赖性细胞毒性。使用分析超速离心和平衡凝胶过滤技术，我们证明两个 FcalphaRI 分子与单个 Fcalpha 同二聚体结合。表面等离子体共振研究证实了结合的 2:1 化学计量，第一次和第二次结合事件的平衡解离常数分别为 176 nM 和 431 nM。在酸性 pH 条件下，结合亲和力降低的方式与结合位点中单个组氨酸残基的质子化一致。热力学分析表明组氨酸残基不参与复合物中的盐桥；事实上，不到 10% 的结合自由能是由静电相互作用贡献的。 FcalphaRI 和 IgA 之间的二价、pH 依赖性相互作用对于 IgA 的细胞因子依赖性吞噬作用以及 FcalphaRI 介导的 IgA 降解或再循环具有重要意义。 (C) 2003 Elsevier Science Ltd. 保留所有权利。
FcalphaRI, the receptor specific for the Fc region of immunoglobulin A (IgA), is responsible for IgA-mediated phagocytosis, oxidative burst, and antibody-dependent cellular cytotoxicity. Using the techniques of analytical ultracentrifugation and equilibrium gel-filtration, we show that two FcalphaRI molecules bind to a single Fcalpha homodimer. Surface plasmon resonance studies confirm the 2:1 stoichiometry of binding, with equilibrium dissociation constants of 176 nM and 431 nM for the first and second binding events, respectively. The binding affinity decreases at acidic pH in a manner consistent with protonation of a single histidine residue in the binding site. A thermodynamic analysis indicates that the histidine residue does not participate in a salt-bridge in the complex; in fact, less than 10% of the free energy of binding was contributed by electrostatic interactions. The bivalent, pH-dependent interaction between FcalphaRI and IgA has important implications for cytokine-dependent phagocytosis of IgA and the FcalphaRI-mediated degradation or recycling of IgA. (C) 2003 Elsevier Science Ltd. All rights reserved.