Structure of the Shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3
Structure of the Shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3
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DOI：
10.1021/bi971806n
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发表时间：
1998-02-17
期刊：
影响因子：
2.9
通讯作者：
Read, RJ
中科院分区：
文献类型：
--
作者：
Ling, H;Boodhoo, A;Read, RJ
志贺样毒素I （SLT-I）是引起人类疾病的大肠杆菌菌株的一种毒力因子，与志贺毒素家族的其他成员一样，它由一个酶(a)亚基和一个结合亚基（b -五聚体）的五个拷贝组成。r -五聚体与靶细胞表面的一种特定的糖脂结合，即globotriaosylneuroide (Gb(3))，因此在毒素的进入中起着至关重要的作用。在2.8埃分辨率下，我们展示了SLT-I b -五聚体与类似的Gb(3)三糖络合的晶体结构，该结构显示出惊人的结合位点密度，每个b -亚基单体有69个残基，三个三糖分子结合在一起。所有15种三糖都与b -五聚体的一侧结合，进一步证明这一侧面向细胞膜。该结构模型与位点定向诱变和碳水化合物类似物结合的数据一致，并允许合理设计治疗性Gb(3)类似物，阻止毒素附着到细胞上。
Shiga-like toxin I (SLT-I) is a virulence factor of Escherichia coli strains that cause disease in humans, Like other members of the Shiga toxin family, it consists of an enzymatic (A) subunit and five copies of a binding subunit (the B-pentamer). The R-pentamer binds to a specific glycolipid, globotriaosylceramide (Gb(3)), on the surface of target cells and thereby plays a crucial role in the entry of the toxin. Here we present the crystal structure at 2.8 Angstrom resolution of the SLT-I B-pentamer complexed with an analogue of the Gb(3) trisaccharide, The structure reveals a surprising density of binding sites, with three trisaccharide molecules bound to each B-subunit monomer of 69 residues. All 15 trisaccharides bind to one side of the B-pentamer, providing further evidence that this side faces the cell membrane. The structural model is consistent with data from site-directed mutagenesis and binding of carbohydrate analogues, and allows the rational design of therapeutic Gb(3) analogues that block the attachment of toxin to cells.