Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor.
Glycan-independent binding and internalization of human IgM to FCMR, its cognate cellular receptor.
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人 IgM 与其同源细胞受体 FCMR 的独立于聚糖的结合和内化
DOI：
10.1038/srep42989
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发表时间：
2017-02-23
影响因子：
4.6
通讯作者：
Pleass RJ
中科院分区：
文献类型：
--
作者：
Lloyd KA;Wang J;Urban BC;Czajkowsky DM;Pleass RJ
免疫球蛋白是第一个在免疫反应中产生的抗体，在中和细菌和病毒方面发挥着重要作用。人免疫球蛋白是高度糖基化的，在μ链上有五个N-连接的糖链位点，在J-链上有一个。已知免疫球蛋白糖基化可调节Fcγ受体的效应功能。相比之下，糖基化对IgM与人Fcμ受体(HFCMR)结合的影响知之甚少。在本研究中，我们将Ig M的Cμ4结构域确定为hFCMR的靶点，并证明hFCMR与Ig M的结合和内化是糖不依赖的。我们为hFCMR生成了一个基于同源的结构，并使用分子动力学模拟来说明这种与IgM的相互作用可能发生的方式。最后，我们揭示了IgM在T细胞增殖中的抑制作用。
IgM is the first antibody to be produced in immune responses and plays an important role in the neutralization of bacteria and viruses. Human IgM is heavily glycosylated, featuring five N-linked glycan sites on the μ chain and one on the J-chain. Glycosylation of IgG is known to modulate the effector functions of Fcγ receptors. In contrast, little is known about the effect of glycosylation on IgM binding to the human Fcμ receptor (hFCMR). In this study, we identify the Cμ4 domain of IgM as the target of hFCMR, and show that binding and internalization of IgM by hFCMR is glycan-independent. We generated a homology-based structure for hFCMR and used molecular dynamic simulations to show how this interaction with IgM may occur. Finally, we reveal an inhibitory function for IgM in the proliferation of T cells.