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Assembly and function of a bacterial genotoxin

Author

Listed:
  • Dragana Nešić

    (Laboratory of Structural Microbiology, The Rockefeller University)

  • Yun Hsu

    (Laboratory of Structural Microbiology, The Rockefeller University)

  • C. Erec Stebbins

    (Laboratory of Structural Microbiology, The Rockefeller University)

Abstract

The tripartite cytolethal distending toxin (CDT) induces cell cycle arrest and apoptosis in eukaryotic cells1,2. The subunits CdtA and CdtC associate with the nuclease CdtB to form a holotoxin that translocates CdtB into the host cell, where it acts as a genotoxin by creating DNA lesions3,4,5,6,7. Here we show that the crystal structure of the holotoxin from Haemophilus ducreyi reveals that CDT consists of an enzyme of the DNase-I family, bound to two ricin-like lectin domains. CdtA, CdtB and CdtC form a ternary complex with three interdependent molecular interfaces, characterized by globular, as well as extensive non-globular, interactions. The lectin subunits form a deeply grooved, highly aromatic surface that we show to be critical for toxicity. The holotoxin possesses a steric block of the CdtB active site by means of a non-globular extension of the CdtC subunit, and we identify putative DNA binding residues in CdtB that are essential for toxin activity.

Suggested Citation

  • Dragana Nešić & Yun Hsu & C. Erec Stebbins, 2004. "Assembly and function of a bacterial genotoxin," Nature, Nature, vol. 429(6990), pages 429-433, May.
    • Handle: RePEc:nat:nature:v:429:y:2004:i:6990:d:10.1038_nature02532
    DOI: 10.1038/nature02532
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    Cited by:

    1. Han-Yi Chen & Wan-Chen Hsieh & Yu-Chieh Liu & Huei-Ying Li & Po-Yo Liu & Yu-Ting Hsu & Shao-Chun Hsu & An-Chi Luo & Wei-Chen Kuo & Yi-Jhen Huang & Gan-Guang Liou & Meng-Yun Lin & Chun-Jung Ko & Hsing-, 2024. "Mitochondrial injury induced by a Salmonella genotoxin triggers the proinflammatory senescence-associated secretory phenotype," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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