L-selectin-carbohydrate interactions: relevant modifications of the Lewis x trisaccharide.
L-selectin-carbohydrate interactions: relevant modifications of the Lewis x trisaccharide.
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L-选择素-碳水化合物相互作用：路易斯 x 三糖的相关修饰。
DOI：
10.1021/bi9613640
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发表时间：
1996
期刊：
影响因子：
2.9
通讯作者：
Kiessling,LL
中科院分区：
文献类型：
--
作者：
Sanders,WJ;Katsumoto,TR;Bertozzi,CR;Rosen,SD;Kiessling,LL
蛋白质−碳水化合物的相互作用被认为是调节细胞−细胞识别和黏附事件的媒介。具体地说，三种称为选择素的碳水化合物结合蛋白(E-、P-和L-选择素)对于白细胞沿血管内皮细胞滚动是必不可少的，这是白细胞从血液中募集到炎症部位或次级淋巴器官的第一步。尽管这一现象已经确立，但人们对它所依赖的分子水平的相互作用知之甚少。这三种选择素都识别Lewis x[Lex： Galβ1→4(Fucα1→3)GlcNAc]和Lewis a[Lea： GalGalβ1→3(Fucα1→4)GlcNAc]三糖核心的硫酸和唾液酸化衍生物，并认为这些结构的变体是选择素识别的碳水化合物决定因素。最近的研究表明，L-选择素的一个分泌的生理配体--粘蛋白GlyCAM-1被唾液酸路易斯x[SLeX： Siaα2→3Galβ1→4(Fucα1→3)GlcNAc]的硫酸盐衍生物封端，并且GlyCAM-1和L-选择素之间的高亲和力需要硫化作用。为了阐明LEX上与L-选择素识别有关的重要位点，我们合成了6个硫酸化的LEX类似物，并测定了它们阻断重组L-选择素−Ig嵌合体与固定化GlyCAM-1的结合的能力。我们的结果表明，6-磺基sLexor与L-选择素的亲和力高于sLexor 6‘-磺基sLex，并且GlyCAM-1上6-位sLexcaping基团的硫酸化对L-选择素的识别是重要的。
Protein−carbohydrate interactions are known to mediate cell−cell recognition and adhesion events. Specifically, three carbohydrate binding proteins termed selectins (E-, P-, and L-selectin) have been shown to be essential for leukocyte rolling along the vascular endothelium, the first step in the recruitment of leukocytes from the blood into inflammatory sites or into secondary lymphoid organs. Although this phenomenon is well-established, little is known about the molecular-level interactions on which it depends. All three selectins recognize sulfated and sialylated derivatives of the Lewis x [Lex: Galβ1→4(Fucα1→3)GlcNAc] and Lewis a [Lea: Galβ1→3(Fucα1→4)GlcNAc] trisaccharide cores with affinities in the millimolar range, and it is believed that variants of these structures are the carbohydrate determinants of selectin recognition. Recently it was shown that the mucin GlyCAM-1, a secreted physiological ligand for L-selectin, is capped with sulfated derivatives of sialyl Lewis x [sLex: Siaα2→3Galβ1→4(Fucα1→3)GlcNAc] and that sulfation is required for the high-affinity interaction between GlyCAM-1 and L-selectin. To elucidate the important sites of sulfation on Lexwith respect to L-selectin recognition, we have synthesized six sulfated Lexanalogs and determined their abilities to block binding of a recombinant L-selectin−Ig chimera to immobilized GlyCAM-1. Our results suggest that 6-sulfo sLexbinds to L-selectin with higher affinity than does sLexor 6‘-sulfo sLexand that sulfation of sLexcapping groups on GlyCAM-1 at the 6-position is important for L-selectin recognition.