Glycoproteomic analysis identifies cryptdin-related sequence 1 as O-glycosylated protein modified with α1,2-fucose in the small intestine
Glycoproteomic analysis identifies cryptdin-related sequence 1 as O-glycosylated protein modified with α1,2-fucose in the small intestine
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DOI：
10.1016/j.abb.2020.108653
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发表时间：
2020-11-30
影响因子：
3.9
通讯作者：
Okajima, Tetsuya
中科院分区：
文献类型：
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作者：
Hashiguchi, Hiroki;Tsukamoto, Yohei;Okajima, Tetsuya
α-1，2-岩藻糖对半乳糖的修饰涉及与肠道细菌的共生和病原菌的清除。据推测，杯状细胞分泌的α-1，2-岩藻糖化粘蛋白参与机体抵御感染，但其详细的分子机制尚不清楚。此前有报道称，小肠潘氏细胞UEA-1凝集素染色呈阳性。然而，携带α-1，2-岩藻糖的Paneth细胞中的糖蛋白尚未被鉴定。回肠裂解产物的糖蛋白质组学分析鉴定了3212个O连接的糖肽和2962个N连接的糖肽。特别是，在Paneth细胞中表达的密码相关序列1(CRS1)被发现是α1，2岩藻糖基化的。与其他抗微生物α-防御素蛋白不同，CRS1含有独特的苏氨酸残基，被O-糖链修饰，其中3HexNAc2Hex1Fuc1NeuAc是主要的糖形式。鉴定在Paneth细胞中表达的CRS1的O-糖链上的α-1，2-岩藻糖，将为进一步了解依赖α-1，2-岩藻糖与肠道细菌共生的机制和消除肠道内的病原菌奠定基础。
The modification of galactose with alpha 1,2-fucose is involved in symbiosis with intestinal bacteria and elimination of pathogenic bacteria. It is postulated that alpha 1,2-fucosylated mucin secreted from goblet cells is involved in defending an organism against infections, but the detailed molecular mechanisms are yet to be elucidated. It was previously reported that Paneth cells of the small intestine were positive for UEA-1 lectin staining. However, glycoproteins in Paneth cells carrying alpha 1,2-fucose have not yet been identified. Glycoproteomic analysis of ileal lysates identified 3212 O-linked and 2962 N-linked glycopeptides. In particular, cryptdin-related sequence 1 (CRS1) expressed in Paneth cells was found to be alpha 1,2-fucosylated. Unlike other antimicrobial alpha-defensin proteins, CRS1 contains unique Thr residues, which are modified with O-glycans, with 3HexNAc2Hex1Fuc1NeuAc being the main glycoform. Identification of alpha 1,2-fucose on the O-glycans of CRS1 expressed in Paneth cells will pave the way for a mechanistic understanding of alpha 1,2-fucose-dependent symbiosis with intestinal bacteria and elimination of pathogenic bacteria in the intestine.