北京大学肖俊宇团队揭示FcμR对免疫球蛋白M的感知
据研究人员介绍，免疫球蛋白M（IgM）是在胚胎发育和体液免疫反应中出现的第一个抗体。IgM可以以几种不同的形式存在，包括B细胞受体（BCR）复合物中的单体、膜结合的IgM、血清中的五聚体和六聚体IgM以及黏膜表面的分泌型IgM。FcμR是哺乳动物中唯一的IgM特异性受体，它能识别不同形式的IgM以调节不同的免疫反应。然而，其背后的分子机制仍然是未知的。
研究人员通过晶体学和低温电子显微镜来描述FcμR-IgM相互作用的结构基础。结果表明，两个FcμR分子与Fcμ-Cμ4二聚体相互作用，表明FcμR能以2:1的比例与膜结合的IgM结合。进一步的分析显示，在IgM BCR的背景下，FcμR的结合点是可以获得的。相比之下，五聚体IgM可以招募四个FcμR分子在同一侧结合，从而促进FcμR寡聚体的形成。这些FcμR分子中的一个占据了分泌成分的结合部位。尽管如此，四个FcμR分子还是与含有分泌成分的分泌型IgM的另一侧结合，这与FcμR在分泌型IgM的逆向运输中的功能一致。这些结果揭示了FcμR感知IgM的复杂机制。
附：英文原文
Title: Immunoglobulin M perception by FcμR
Author: Li, Yaxin, Shen, Hao, Zhang, Ruixue, Ji, Chenggong, Wang, Yuxin, Su, Chen, Xiao, Junyu
Issue&Volume: 2023-03-22
Abstract: Immunoglobulin M (IgM) is the first antibody to emerge during embryonic development and the humoral immune response1. IgM can exist in several distinct forms, including monomeric, membrane-bound IgM within the B cell receptor (BCR) complex, pentameric and hexameric IgM in serum and secretory IgM on the mucosal surface. FcμR, the only IgM-specific receptor in mammals, recognizes different forms of IgM to regulate diverse immune responses2,3,4,5. However, the underlying molecular mechanisms remain unknown. Here we delineate the structural basis of the FcμR–IgM interaction by crystallography and cryo-electron microscopy. We show that two FcμR molecules interact with a Fcμ-Cμ4 dimer, suggesting that FcμR can bind to membrane-bound IgM with a 2:1 stoichiometry. Further analyses reveal that FcμR-binding sites are accessible in the context of IgM BCR. By contrast, pentameric IgM can recruit four FcμR molecules to bind on the same side and thereby facilitate the formation of an FcμR oligomer. One of these FcμR molecules occupies the binding site of the secretory component. Nevertheless, four FcμR molecules bind to the other side of secretory component-containing secretory IgM, consistent with the function of FcμR in the retrotransport of secretory IgM. These results reveal intricate mechanisms of IgM perception by FcμR.
DOI: 10.1038/s41586-023-05835-w
Source: https://www.nature.com/articles/s41586-023-05835-w
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
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