Oligomeric and subunit structure of the Helicobacter pylori vacuolating cytotoxin.
Oligomeric and subunit structure of the Helicobacter pylori vacuolating cytotoxin.
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DOI：
10.1083/jcb.133.4.801
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发表时间：
1996-05
期刊：
影响因子：
--
通讯作者：
Telford JL
中科院分区：
文献类型：
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作者：
Lupetti P;Heuser JE;Manetti R;Massari P;Lanzavecchia S;Bellon PL;Dallai R;Rappuoli R;Telford JL
与疾病相关的幽门螺杆菌菌株会产生一种强烈的毒素，据信这种毒素在人类消化性溃疡疾病中发挥关键作用。在体外，这种毒素会导致靶细胞严重的空泡变性，因此被称为VacA(空泡毒素A)。细胞毒活性与一种由95kD多肽的几个拷贝组成的600-kD蛋白有关，这种多肽从细菌释放后经历特定的蛋白水解性切割，产生37-kD和58-kD片段。快速冷冻，深蚀刻电子显微镜显示，天然细胞毒素形成规则的低聚物，具有六或七重径向对称。在每个单体中，可以清楚地区分两个结构域，这表明37-kD和58-kD片段来自于单体不同亚基之间的蛋白水解性切割。对广泛切割成37-和58-kD亚基的毒素制剂的分析支持这一解释，并揭示了在切割后，亚基仍与寡聚体结构相关联。这些数据表明，它在结构上与AB型毒素相似。
Disease-associated strains of Helicobacter pylori produce a potent toxin that is believed to play a key role in peptic ulcer disease in man. In vitro the toxin causes severe vacuolar degeneration in target cells and has thus been termed VacA (for vacuolating cytotoxin A). Cytotoxic activity is associated with a > 600-kD protein consisting of several copies of a 95-kD polypeptide that undergoes specific proteolytic cleavage after release from the bacteria to produce 37- and 58-kD fragments. Quick freeze, deep etch electron microscopy has revealed that the native cytotoxin is formed as regular oligomers with either six- or seven-fold radial symmetry. Within each monomer, two domains can clearly be distinguished, suggesting that the 37- and 58-kD fragments derive from proteolytic cleavage between discrete subunits of the monomer. Analysis of preparations of the toxin that had undergone extensive cleavage into the 37- and 58-kD subunits supports this interpretation and reveals that after cleavage the subunits remain associated in the oligomeric structure. The data suggest a structural similarity with AB-type toxins.