Crystal structure of the MazE/MazF complex: Molecular bases of antidote-toxin recognition

A structure of the Escherichia coli chromosomal MazE/MazF addiction module has been determined at 1.7 Angstrom resolution. Addiction modules consist of stable toxin and unstable antidote proteins that govern bacterial cell death. MazE (antidote) and MazF (toxin) form a linear heterohexamer composed of alternating toxin and antidote homodimers (MazF(2)-MazE(2)-MazF(2)). The MazE homodimer contains a beta barrel from which two extended C termini project, making interactions with flanking MazF homodimers that resemble the plasmid-encoded toxins CcdB and Kid. The MazE/MazF heterohexamer structure documents that the mechanism of antidote-toxin recognition is common to both chromosomal and plasmid-borne addiction modules, and provides general molecular insights into toxin function, antidote degradation in the absence of toxin, and promoter DNA binding by antidote/toxin complexes.