1SR4

Crystal Structure of the Haemophilus ducreyi cytolethal distending toxin

Summary for 1SR4

• Entry DOI: 10.2210/pdb1sr4/pdb
• Descriptor: Cytolethal distending toxin subunit A, cytolethal distending toxin protein B, cytolethal distending toxin protein C, ... (5 entities in total)
• Functional Keywords: toxin, bacterial, haemophilus ducreyi, virulence, dna damage, genotoxin, cytotoxins, cell cycle, apoptosis, lectin, deoxyribonuclease i
• Biological source: Haemophilus ducreyi; More
• Cellular location: Cell outer membrane; Lipid-anchor (Probable): O06522
• Total number of polymer chains: 3
• Total formula weight: 72320.42

Authors

Nesic, D.,Hsu, Y.,Stebbins, C.E. (deposition date: 2004-03-22, release date: 2004-06-15, Last modification date: 2024-11-06)

Primary citation

Nesic, D.,Hsu, Y.,Stebbins, C.E.
Assembly and Function of a Bacterial Genotoxin
Nature, 429:429-433, 2004

PubMed Abstract: The tripartite cytolethal distending toxin (CDT) induces cell cycle arrest and apoptosis in eukaryotic cells. 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 lesions. 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.

PubMed: 15164065
DOI: 10.1038/nature02532

Experimental method

X-RAY DIFFRACTION (2 Å)