Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor(,).
Crystal structure and immunoglobulin G binding properties of the human major histocompatibility complex-related Fc receptor(,).
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DOI：
10.1021/bi000749m
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发表时间：
2000-08
期刊：
影响因子：
2.9
通讯作者：
and Anthony P. West;Pamela J. Bjorkman
中科院分区：
文献类型：
--
作者：
and Anthony P. West;Pamela J. Bjorkman
新生儿Fc受体（FcRn）执行两种不同但相关的功能：将母体免疫球蛋白G（IgG）转运至新生儿前哺乳动物或新生儿哺乳动物，从而提供被动免疫，以及保护IgG免受正常血清蛋白酶的影响。FcRn与I类MHC蛋白相关，但缺乏功能性肽结合沟。人FcRn的晶体结构已在2.7 A分辨率下测定，并与先前描述的大鼠FcRn的结构[Burmeister等（1994）Nature 372，336-343]以及MHC和MHC相关蛋白的结构进行比较。人FcRn在结构上类似于大鼠受体，但在晶体中不形成受体二聚体，如在大鼠FcRn晶体中观察到的。人FcRn和IgG之间的相互作用通过使用平衡凝胶过滤确定结合化学计量和通过使用表面等离子体共振测定推导不同人IgG亚类的结合亲和力来表征。与大鼠和小鼠FcRn一样，人FcRn以2：1的受体：配体化学计量与IgG相互作用。人FcRn与四种人IgG亚类的结合显示亚类和同种异型变化，但没有与血清半衰期相关的明确亚类亲和力差异。人FcRn的结构及其配体结合的研究与目前使用FcRn介导的血清中IgG半衰期调节以增加基于抗体的治疗剂的寿命的努力相关。
The neonatal Fc receptor (FcRn) performs two distinct but related functions: transport of maternal immunoglobulin G (IgG) to pre- or neonatal mammals, thus providing passive immunity, and protection of IgG from normal serum protein catabolism. FcRn is related to class I MHC proteins but lacks a functional peptide binding groove. The crystal structure of human FcRn has been determined at 2.7 A resolution and compared to the previously described structure of rat FcRn [Burmeister et al. (1994) Nature 372, 336-343] and to the structures of MHC and MHC-related proteins. Human FcRn is structurally similar to the rat receptor but does not form receptor dimers in the crystals as observed in crystals of rat FcRn. The interaction between human FcRn and IgG was characterized by determining the binding stoichiometry using equilibrium gel filtration and by deriving binding affinities for the different human IgG subclasses using a surface plasmon resonance assay. Like rat and mouse FcRn, human FcRn interacts with IgG with a 2:1 receptor:ligand stoichiometry. The binding of human FcRn to the four human IgG subclasses shows subclass and allotype variations but no clear subclass affinity differences that correlate with serum half-lives. The structure of human FcRn and studies of its ligand binding are relevant to current efforts to use FcRn-mediated regulation of IgG half-life in serum to increase the lifetimes of antibody-based therapeutics.