Structure-function analysis of large clostridial cytotoxins

大梭菌细胞毒素的结构-功能分析

• 批准号: 5437441
• 负责人: Professor Dr. Klaus Aktories
• 金额: --
• 依托单位: Institut für Experimentelle und Klinische Pharmakologie,Toxikologie und Naturheilkunde
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2004
• 资助国家: 德国
• 起止时间: 2003-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5437441?language=en
• 关键词: Structure; function; analysis; large; clostridial

Clostridial glycosylating toxins are important virulence factors causally involved in diseases. They play pivotal roles as pathogenic factors of antibiotics-associated diarrhea and pseudomembranous colitis. In spite of large progress in the analysis of the structure-function-relationship of the toxins, questions of toxin up-take and receptor binding are largely unsolved. To answer these questions, a new short glycosylating toxin (TpeL) from C. perfringens is employed. This toxin has no typical C-terminal receptor binding domain but is still cytotoxic. First studies with a gene trapping method on the basis of haploid cells, resulted in identification of a membrane receptor from the LDL receptor family. The interaction of the toxin with the receptor will be characterized and the role of the receptor in up-take of the toxin studied. It will be analyzed by gene-trapping whether other clostridial glycosylating toxins use the same type of receptors. The identification of membrane receptors is crucial for understanding the mode of action of the toxins and for the development of new therapeutic strategies.

梭菌糖基化毒素是与疾病相关的重要毒力因子。它们作为抗生素相关性腹泻和伪膜性结肠炎的致病因素发挥着关键作用。尽管在毒素的结构-功能关系的分析方面取得了巨大进展，但毒素摄取和受体结合的问题在很大程度上尚未得到解决。为了回答这些问题，我们使用了产气荚膜梭菌中的一种新的短糖基化毒素 (TpeL)。该毒素没有典型的 C 末端受体结合结构域，但仍然具有细胞毒性。第一项基于单倍体细胞的基因捕获方法研究，从 LDL 受体家族中鉴定出了一种膜受体。将表征毒素与受体的相互作用，并研究受体在毒素吸收中的作用。将通过基因捕获分析其他梭菌糖基化毒素是否使用相同类型的受体。膜受体的识别对于理解毒素的作用模式和开发新的治疗策略至关重要。

项目成果

Rho-modifying bacterial protein toxins.

Rho 修饰细菌蛋白毒素。

• DOI: 10.1093/femspd/ftv091
• 发表时间: 2015-12-01
• 期刊: Pathogens and disease
• 作者: K. Aktories

The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B

• DOI: 10.1073/pnas.1807658115
• 发表时间: 2018-09-04
• 期刊: Proceedings of the National Academy of Sciences
• 作者: Marcus Steinemann;A. Schlosser;T. Jank;K. Aktories
• 通讯作者: K. Aktories

LRP1 is a receptor for Clostridium perfringens TpeL toxin indicating a two-receptor model of clostridial glycosylating toxins

LRP1 是产气荚膜梭菌 TpeL 毒素的受体，表明梭菌糖基化毒素的双受体模型

• DOI: 10.1073/pnas.1323790111
• 发表时间: 2014-04-15
• 期刊: Proceedings of the National Academy of Sciences
• 作者: B. Schorch;Shuo Song;Ferdy R. van Diemen;H. Bock;Petra May;J. Herz;T. Brummelkamp;P. Papatheodorou
• 通讯作者: P. Papatheodorou

Targeting oncogenic Ras by the Clostridium perfringens toxin TpeL

产气荚膜梭菌毒素 TpeL 靶向致癌 Ras

• DOI: 10.18632%2foncotarget.24740
• 发表时间: 2018
• 期刊: Oncotarget
• 作者: Schorch B; Heni H; Zahaf NI; Brummer T; Mione M; Schmidt G; Papatheodorou P; Aktories K
• 通讯作者: Aktories K

Novel receptors for bacterial protein toxins.

细菌蛋白毒素的新型受体。

• DOI: 10.1016/j.mib.2014.11.003
• 发表时间: 2015-02-01
• 期刊: Current opinion in microbiology
• 影响因子: 5.4
• 作者: G. Schmidt;P. Papatheodorou;K. Aktories
• 通讯作者: K. Aktories