Crystal structure of the plasmid maintenance system : Functional mechanism of toxin and inactivation by 2 2 complex formation

Programmed cell death in prokaryotes is frequently found as postsegregational killing. It relies on antitoxin toxin systems that secure stable inheritance of low and medium copy number plasmids during cell division and kill cells that have lost the plasmid. The broad-host-range, low-copy-number plasmid pSM19035 from Streptococcus pyogenes carries the genes encoding the antitoxin toxin system and antibiotic resistance proteins, among others. The crystal structure of the biologically nontoxic 2 2 protein complex at a 1.95-Å resolution and site-directed mutagenesis showed that free acts as phosphotransferase by using ATP GTP. In 2 2, the toxin is inactivated because the N-terminal helix of the antitoxin blocks the ATP GTP-binding site. To our knowledge, this is the first prokaryotic postsegregational killing system that has been entirely structurally characterized.