Differences between Human and Mouse IgM Fc Receptor (FcµR).

Differences between Human and Mouse IgM Fc Receptor (FcµR).
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DOI:
10.3390/ijms22137024
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发表时间:
2021-06-29
影响因子:
5.6
通讯作者:
Sutton BJ
Sutton BJ
中科院分区:
生物学2区
文献类型:
--
作者:
Kubagawa H;Skopnik CM;Al-Qaisi K;Calvert RA;Honjo K;Kubagawa Y;Teuber R;Aliabadi PM;Enghard P;Radbruch A;Sutton BJ

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非免疫“天然”和抗原诱导的“免疫”IgM对于保护免受病原体侵害和调节对自身抗原的免疫反应都很重要。自2009年通过功能性克隆策略在人类中鉴定出真正的IgM Fc受体(FcµR)以来,已开始探索FcµR在这些IgM效应子功能中的作用。在这篇短文中,我们描述了人类和小鼠Fcµ R在识别过程、细胞分布和配体结合活性方面的差异,重点是我们最近从人类FcµR突变分析中发现的结果。我们已经确定了人FcµR的至少三个位点,即,CDR 2中的Asn 66、DE环中的Lys 79至Arg 83和CDR 3中的Asn 109负责其组成性IgM-配体结合。计算结构建模分析的结果与这些突变数据一致,并提出了人FcµR的配体结合Ig样结构域的模型。偶然地,用小鼠等同物Gln和Leu取代人FcµR的CDR 1中的Glu 41和Met 42,无论是单独还是更显著地组合,都增强了受体表达和IgM结合。这些发现将有助于未来开发针对FcµR的预防和治疗干预措施。
Both non-immune “natural” and antigen-induced “immune” IgM are important for protection against pathogens and for regulation of immune responses to self-antigens. Since the bona fide IgM Fc receptor (FcµR) was identified in humans by a functional cloning strategy in 2009, the roles of FcµR in these IgM effector functions have begun to be explored. In this short essay, we describe the differences between human and mouse FcµRs in terms of their identification processes, cellular distributions and ligand binding activities with emphasis on our recent findings from the mutational analysis of human FcµR. We have identified at least three sites of human FcµR, i.e., Asn66 in the CDR2, Lys79 to Arg83 in the DE loop and Asn109 in the CDR3, responsible for its constitutive IgM-ligand binding. Results of computational structural modeling analysis are consistent with these mutational data and a model of the ligand binding, Ig-like domain of human FcµR is proposed. Serendipitously, substitution of Glu41 and Met42 in the CDR1 of human FcµR with mouse equivalents Gln and Leu, either single or more prominently in combination, enhances both the receptor expression and IgM binding. These findings would help in the future development of preventive and therapeutic interventions targeting FcµR.
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