Definitive evidence that a single N-glycan among three glycans on inducible costimulator is required for proper protein trafficking and ligand binding
Definitive evidence that a single N-glycan among three glycans on inducible costimulator is required for proper protein trafficking and ligand binding
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DOI：
10.1016/j.bbrc.2009.11.098
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Tsuji, Takashi
中科院分区：
文献类型：
--
作者：
Kamei, Naoki;Fukui, Rie;Tsuji, Takashi
糖基化是一种广泛存在于糖蛋白中的翻译后修饰，多糖在蛋白质折叠中起着关键作用。然而，目前尚不清楚是否蛋白质糖基化的所有位置都参与了聚糖的功能，或者特定位置是否有单独的作用。在这里，我们证明了在三种聚糖中，一种特定的n -聚糖参与了油诱导共刺激（ICOS），一种t细胞共刺激分子。我们发现糖基化缺陷突变蛋白在氨基酸位置89 （N89）缺乏n-聚糖。但不包括缺乏N23或N110的蛋白质。额外的证据表明N89糖基化间接参与ICOS配体结合。这些数据表明，在三个推测的ICOS糖基化位点中，N89是在内质网中适当的ICOS蛋白折叠、细胞内运输和配体结合活性所必需的。这项研究为当前对糖蛋白的多种聚糖中特定n -聚糖的必要性和潜在功能的机制理解做出了重大贡献。(C) 2009 Elsevier Inc .版权所有
Glycosylation is a widespread post-translational modification Found in glycoproteins Glycans play key roles in protein folding. quality control in the endoplasmic reticulum (ER) and protein trafficking within cells However, it remains unclear whether all positions of protein glycosylation are involved in glycan functions, or if specific positions have individual roles Here we demonstrate the integral involvement of a specific N-glycan from amongst the three glycans present oil inducible costimulator (ICOS), a T-cell costimulatory molecule. in proper protein folding and intracellular trafficking to the cell surface membrane We found that glycosylation-defective mutant proteins lacking N-glycan at amino-acid position 89 (N89). but not proteins lacking either N23 or N110. were retained within the cell and were not detected oil the cell surface membrane Additional evidence Suggested that N89 glycosylation was indirectly involved in ICOS ligand binding These data suggest that amongst the three putative ICOS glycosylation sites, N89 is requried for proper ICOS protein folding in the ER, intracellular trafficking and ligand binding activity. This study represents a substantial contribution to the current mechanistic understanding of the necessity and potential functions of a specific N-glycan among the multiple glycans of glycoproteins. (C) 2009 Elsevier Inc All rights reserved