Structural diversity and specific distribution of 0-glycans in normal human mucins along the intestinal tract
Structural diversity and specific distribution of 0-glycans in normal human mucins along the intestinal tract
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DOI：
10.1042/bj20040605
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发表时间：
2004-12-01
影响因子：
4.1
通讯作者：
Michalski, JC
中科院分区：
文献类型：
--
作者：
Robbe, C;Capon, C;Michalski, JC
从两个具有血型AL e（B）（A-Lewis（B））的个体中分离来自肠道不同部分（回肠、盲肠、横结肠和乙状结肠以及直肠）的纯化人粘蛋白。碱性硼氢化物处理后，释放的低聚糖的结构特征的纳米ESI Q-TOF MS/MS（电喷雾电离四极杆飞行时间串联MS），没有事先分馏或衍生化。超过100种不同的寡糖，多达10个单糖残基，使用这种技术进行了鉴定。基于核心3结构的寡聚体，GlcNAc（β 1 -3）GalNAc（其中GlcNAc是N-乙酰基-D-葡糖胺，GalNAc是N-乙酰基半乳糖胺），广泛分布于人肠粘蛋白中。核心5结构，GalNAc（α 1 -3）GalNAc，也在所有馏分中回收。此外，在聚糖和末端表位的大小、多样性和表达方面，寡糖库的比较显示高水平的粘蛋白特异性糖基化：特别是在小肠中发现的高度岩藻糖基化的聚糖主要基于核心4结构，GlcNAc（β 1 -3）[GlcNAc（β 1 -6）]GalNAc，而携带核心2聚糖的磺基-Lex决定簇，Gal（β 1 -3）[GlcNAc（β 1 -6）]- GalNAc（其中Gal为半乳糖）主要在远端结肠中回收。H和A血型抗原决定簇仅存在于回肠和盲肠中，而发现Sd（a）/Cad血型相关表位GalNAc（β 1 -4）[NeuAc（α 2 -3）]Gal（其中NeuAc是N-乙酰神经氨酸）沿沿着结肠长度增加。我们的研究结果表明粘蛋白为微生物创造了一个巨大的潜在结合位点库，这可以解释人类肠道中细菌的区域特异性定植。
Purified human mucins from different parts of the intestinal tract (ileum, cecum, transverse and sigmoid colon and rectum) were isolated from two individuals with blood group ALe(b) (A-Lewis(b)). After alkaline borohydride treatment the released oligosaccharides were structurally characterized by nano-ESI Q-TOF MS/MS (electrospray ionization quadrupole time-of-flight tandem MS) without prior fractionation or derivatization. More than 100 different oligosaccharides, with up to ten monosaccharide residues, were identified using this technique. Oligosaccharides based on core 3 structures, GlcNAc(beta1-3)GalNAc (where GlcNAc is N-acetyl-D-glucosamine and GalNAc is N-acetylgalactosamine), were widely distributed in human intestinal mucins. Core 5 structures, GalNAc(alpha1-3)GalNAc, were also recovered in all fractions. Moreover, a comparison of the oligosaccharide repertoire, with respect to size, diversity and expression of glycans and terminal epitopes, showed a high level of mucin-specific glycosylation: highly fucosylated glycans, found specifically in the small intestine, were mainly based on core 4 structures, GlcNAc(beta1-3)[GlcNAc(beta1-6)]GalNAc, whereas the sulpho-Lex determinant carrying core 2 glycans, Gal(beta1-3)[GlcNAc(beta1-6)]- GalNAc (where Gal is galactose), was recovered mainly in the distal colon. Blood group H and A antigenic determinants were present exclusively in the ileum and cecum, whereas blood group Sd(a)/Cad related epitopes, GalNAc(beta1-4)[NeuAc(alpha2-3)]Gal (where NeuAc is N-acetylneuraminate), were found to increase along the length of the colon. Our findings suggest that mucins create an enormous repertoire of potential binding sites for microorganisms that could explain the regio-specific colonization Of bacteria in the human intestinal tract.