Assembly and function of a bacterial genotoxin

Dragana Nešić, Yun Hsu and C. Erec Stebbins ()
Additional contact information
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

Nature, 2004, vol. 429, issue 6990, 429-433

Abstract: 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.

Date: 2004
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature02532 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:429:y:2004:i:6990:d:10.1038_nature02532

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature02532

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().