Structural Basis for Toxin Inhibition in the VapXD Toxin-Antitoxin System

Summary Bacterial type II toxin-antitoxin (TA) modules encode a toxic protein that downregulates metabolism and specific antitoxin binds inhibits the toxin during normal growth. In non-typeable Haemophilus influenzae, common cause of infections in humans, vapXD locus was found to constitute functional TA module contribute pathogenicity; however, mode action VapD mechanism inhibition by VapX remain unknown. Here, we report structure intact H. influenzae VapXD complex, revealing an unusual 2:1 molecular stoichiometry where Cas2-like homodimer single antitoxin. consists oligonucleotide/oligosaccharide-binding domain docks into asymmetrical cavity on dimer. Structures isolated further reveal how symmetrical adapts interacting with suggest primordial system evolved become part CRISPR-Cas immunity systems.