B-cell maturation antigen is modified by a single N-glycan chain that modulates ligand binding and surface retention
B-cell maturation antigen is modified by a single N-glycan chain that modulates ligand binding and surface retention
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DOI：
10.1073/pnas.1309417110
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发表时间：
2013-07-02
影响因子：
11.1
通讯作者：
Lin, Kuo-I
中科院分区：
文献类型：
--
作者：
Huang, Han-Wen;Chen, Chein-Hung;Lin, Kuo-I
糖基化是一种重要的翻译后修饰过程，可以调节蛋白质的结构和功能，但其对浆细胞特性的影响尚不清楚。在这项研究中，我们通过与浆细胞中的炔基糖类似物的点击反应结合质谱分析鉴定了一组糖蛋白。 B 细胞成熟抗原 (BCMA) 是维持浆细胞存活的必需膜蛋白，被鉴定为在单个 N-糖基化位点天冬酰胺 42 上表现出复合型 N-聚糖的糖蛋白。然后，我们研究了 N-糖基化对 BCMA 功能的影响，发现地塞米松诱导的恶性浆细胞凋亡可以通过用 BCMA 配体（例如增殖诱导配体）治疗来挽救(APRIL) 和 B 细胞激活因子 (BAFF)，而浆细胞末端唾液酸的去除进一步增强了配体介导的保护。这种效应与 BCMA 表面保留的增加有关，导致其在细胞表面的水平升高。此外，在体外结合测定中，α1-3,-4岩藻糖基化（而非末端唾液酸化）有助于BCMA与配体的结合。总之，我们的结果强调了 BCMA 上的 N-糖基化在调节配体结合和浆细胞功能中的重要性。
Glycosylation, an important posttranslational modification process, can modulate the structure and function of proteins, but its effect on the properties of plasma cells is largely unknown. In this study, we identified a panel of glycoproteins by click reaction with alkynyl sugar analogs in plasma cells coupled with mass spectrometry analysis. The B-cell maturation antigen (BCMA), an essential membrane protein for maintaining the survival of plasma cells, was identified as a glycoprotein exhibiting complex-type N-glycans at a single N-glycosylation site, asparagine 42. We then investigated the effect of N-glycosylation on the function of BCMA and found that the dexamethasone-induced apoptosis in malignant plasma cells can be rescued by treatment with BCMA ligands, such as a proliferationinducing ligand (APRIL) and B-cell-activating factor (BAFF), whereas removal of terminal sialic acid on plasmacells further potentiated the ligand-mediated protection. This effect is associated with the increased surface retention of BCMA, leading to its elevated level on cell surface. In addition, the alpha 1-3,-4 fucosylation, but not the terminal sialylation, assists the binding of BCMA with ligands in an in vitro binding assay. Together, our results highlight the importance of N-glycosylation on BCMA in the regulation of ligand binding and functions of plasma cells.