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首页> 外文期刊>Reviews of physiology, biochemistry and pharmacology. >Large clostridial cytotoxins
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Large clostridial cytotoxins

机译：大梭菌细胞毒素

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摘要

The large clostridial cytotoxins are a family of structurally and functionally related exotoxins from Clostridium difficile (toxins A and B), C. sordellii (lethal and hemorrhagic toxin) and C. novyi (α-toxin). The exotoxins are major pathogenicity factors which in addition to their in vivo effects are cytotoxic to cultured cell lines causing reorganization of the cytoskeleton accompanied by morphological changes. The exotoxins are single-chain protein toxins, which are constructed of three domains: receptor-binding, translocation and catalytic domain. These domains reflect the self-mediated cell entry via receptor-mediated endocytosis, translocation into the cytoplasm, and execution of their cytotoxic activity by an inherent enzyme activity. Enzymatically, the toxins catalyze the transfer of a glucosyl moiety from UDP-glucose to the intracellular target proteins which are the Rho and Ras GTPases. The covalent attachment of the glucose moiety to a conserved threonine within the effector region of the GTPases renders the Rho-GTPases functionally inactive. Whereas the molecular mode of cytotoxic effects is fully understood, the mechanisms leading to inflammatory processes in the context of disease (e.g., antibiotic-associated pseudomembranous colitis caused by Clostridium difficile) are less clear.
机译：大型梭菌细胞毒素是来自艰难梭菌（毒素A和B），索氏梭菌（致命和出血性毒素）和新孢梭菌（α-毒素）的结构和功能相关的外毒素家族。外毒素是主要的致病性因子，除其体内作用外，对培养的细胞系具有细胞毒性，引起细胞骨架重组并伴随形态变化。外毒素是单链蛋白毒素，由三个域构成：受体结合域，易位域和催化域。这些结构域通过受体介导的内吞作用反映自身介导的细胞进入，易位进入细胞质，并通过固有的酶活性执行其细胞毒活性。酶促地，该毒素催化糖基部分从UDP葡萄糖转移到细胞内靶蛋白，即Rho和Ras GTPases。葡萄糖部分与GTP酶的效应子区域内保守的苏氨酸的共价连接使Rho-GTP酶功能失活。尽管细胞毒作用的分子模式已被完全理解，但是在疾病（例如由艰难梭菌引起的与抗生素相关的假膜性结肠炎）的背景下导致炎症过程的机制尚不清楚。

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