面对糖鞘脂类与志贺毒素的相互作用：人血管内皮细胞的困境。
Facing glycosphingolipid-Shiga toxin interaction: dire straits for endothelial cells of the human vasculature.
机构信息
Institute for Hygiene, University of Münster, Robert-Koch-Str. 41, 48149, Münster, Germany.
出版信息
Cell Mol Life Sci. 2013 Feb;70(3):425-57. doi: 10.1007/s00018-012-1060-z. Epub 2012 Jul 6.
Abstract
The two major Shiga toxin (Stx) types, Stx1 and Stx2, produced by enterohemorrhagic Escherichia coli (EHEC) in particular injure renal and cerebral microvascular endothelial cells after transfer from the human intestine into the circulation. Stxs are AB(5) toxins composed of an enzymatically active A subunit and the pentameric B subunit, which preferentially binds to the glycosphingolipid globotriaosylceramide (Gb3Cer/CD77). This review summarizes the current knowledge on Stx-caused cellular injury and the structural diversity of Stx receptors as well as the initial molecular interaction of Stxs with the human endothelium of different vascular beds. The varying lipoforms of Stx receptors and their spatial organization in lipid rafts suggest a central role in different modes of receptor-mediated endocytosis and intracellular destiny of the toxins. The design and development of tailored Stx neutralizers targeting the oligosaccharide-toxin recognition event has become a very real prospect to ameliorate or prevent life-threatening renal and neurological complications.
摘要
两种主要的志贺毒素（Stx）类型，Stx1 和 Stx2，由肠出血性大肠杆菌（EHEC）产生，特别是在从人体肠道转移到循环系统后，会损伤肾和脑微血管内皮细胞。Stxs 是由一个酶活性 A 亚基和五聚体 B 亚基组成的 AB(5)毒素，优先与糖鞘脂神经节苷脂 Gb3Cer/CD77 结合。这篇综述总结了 Stx 引起的细胞损伤以及 Stx 受体的结构多样性，以及 Stx 与不同血管床的人内皮细胞的初始分子相互作用。Stx 受体的不同脂类形式及其在脂筏中的空间组织表明，它们在受体介导的胞吞作用的不同模式和毒素的细胞内命运中发挥核心作用。针对寡糖-毒素识别事件设计和开发定制的 Stx 中和剂已成为改善或预防危及生命的肾和神经并发症的非常现实的前景。
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