LIPID MODULATION OF GLYCOLIPID RECEPTOR FUNCTION - AVAILABILITY OF GAL(ALPHA-1-4)GAL DISACCHARIDE FOR VEROTOXIN BINDING IN NATURAL AND SYNTHETIC GLYCOLIPIDS

LIPID MODULATION OF GLYCOLIPID RECEPTOR FUNCTION - AVAILABILITY OF GAL(ALPHA-1-4)GAL DISACCHARIDE FOR VEROTOXIN BINDING IN NATURAL AND SYNTHETIC GLYCOLIPIDS
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DOI:
10.1111/j.1432-1033.1994.tb19064.x
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发表时间:
1994-08-01
期刊:
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子:
--
通讯作者:
LINGWOOD, CA
LINGWOOD, CA
中科院分区:
其他
文献类型:
--
作者:
BOYD, B;MAGNUSSON, G;LINGWOOD, CA

文献摘要

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Verotoxins与含有末端Gal(α 1-4)Gal残基的鞘糖脂结合。三己糖神经酰胺在体外是verotoxin-1最有效的受体,并且是介导大多数敏感细胞的细胞病理学的功能性质膜受体。verotoxin-1与一系列含半乳糖或含三己糖的合成糖脂结合,其中单烷基硫化物和双烷基硫化物或砜作为脂质部分,已经通过TLC覆盖和在辅助脂质存在下在固相中研究了毒素结合。结果表明,对于相同的碳水化合物,根据脂质部分的性质,结合显着改变。半乳糖序列和疏水物种的紧密接近也损害了recognition.The脂质环境也是受体功能的主要决定因素,因为物种是有效的,即使是首选的毒素受体,通过TLC覆盖监测,不一定在辅助脂质的存在下识别。某些糖脂,这是不承认的薄层色谱覆盖,然而,被发现是有效的受体在辅助脂质matrix.These结果表明verotoxin/糖脂识别的脂质部分的关键作用,并讨论有关毒素发病机制和糖脂受体功能。
Verotoxins bind to glycosphingolipids containing terminal Gal(alpha 1-4)Gal residues. Globotriaosyl-ceramide is the most effective receptor for verotoxin-1 in vitro and is the functional plasma-membrane receptor which mediates cytopathology for most sensitive cells, Binding of verotoxin-1 to a series of galabiose-containing or globotriaose-containing synthetic glycolipids with monoalkylsulfides and bisalkylsulfides or sulfones as the lipid moiety, have been studied for toxin binding by TLC overlay and in solid phase in the presence of auxiliary lipids. The results demonstrate that for an identical carbohydrate, binding is dramatically altered according to the nature of the lipid moiety. The close proximity of the galabiose sequence and the hydrophobic species also compromised recognition.The lipid environment is also a major determinant of receptor function, since species that were effective, even preferred toxin receptors as monitored by TLC overlay, were not necessarily recognized in the presence of auxiliary lipids. Certain glycolipids, which were not recognized by TLC overlay, were nevertheless found to be effective receptors in an auxiliary lipid matrix.These results demonstrate the crucial role of the lipid moiety in verotoxin/glycolipid recognition and are discussed in relation to toxin pathogenesis and glycolipid receptor function.