GLUCOSYLATION OF RHO-PROTEINS BY CLOSTRIDIUM-DIFFICILE TOXIN-B
GLUCOSYLATION OF RHO-PROTEINS BY CLOSTRIDIUM-DIFFICILE TOXIN-B
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DOI：
10.1038/375500a0
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发表时间：
1995-06-08
期刊：
影响因子：
64.8
通讯作者：
AKTORIES, K
中科院分区：
文献类型：
--
作者：
JUST, I;SELZER, J;AKTORIES, K
毒素A和B是艰难梭菌的主要毒力因子，是肠源性假膜性结肠炎的病原体。在培养的细胞系中，其强效细胞毒性源自其诱导微丝细胞骨架解聚的能力（1，2）。毒素B作用于低分子量GTdR RhoA（3，4），其参与肌动蛋白细胞骨架的调节。我们在这里报告，毒素B催化的掺入高达1摩尔葡萄糖每摩尔的RhoA的氨基酸苏氨酸在位置37。通过串联电喷雾质谱鉴定和定位修饰。UDP-葡萄糖选择性地充当毒素B催化的单葡萄糖基化反应的共底物。微量注射RhoA先前葡糖基化毒素B到单层细胞引起的肌动蛋白丝解聚，表明显性负活性的葡糖基化RhoA。
TOXIN A and B, the major virulence factors of Clostridium difficile, are the causative agents of antibiotic-associated pseudomembranous colitis. In cultured cell lines their potent cytotoxicity results from their ability to induce disaggregation of the microfilament cytoskeleton(1,2). Toxin B acts on the low-molecular-mass GTPase RhoA(3,4), which is involved in the regulation of the actin cytoskeleton. We report here that toxin B catalyses the incorporation of up to one mole of glucose per mole of RhoA at the amino acid threonine at position 37. The modification was identified and localized by tandem electrospray mass spectrometry. UDP-glucose selectively serves as cosubstrate for the monoglucosylation reaction catalysed by toxin B. Microinjection of RhoA previously glucosylated by toxin B into monolayer cells caused disaggregation of actin filaments, indicating a dominant-negative activity of glucosylated RhoA.