The Bacillus anthracis virulence regulator AtxA controls transcription of more than a hundred genes including those encoding major virulence factors and capsule biosynthesis. The transcription of atxA gene is affected by temperature, redox potential, growth phase, and the presence of glucose. Additionally, the AtxA activity is regulated by phosphorylation of two specific histidines, H199 and H379.
The AtxA crystal structure is multimodular with five distinct domains: two N-terminal DNA-binding domains, two PRDs (phosphoenolpyruvate phosphotransferase system regulation domains) and a C-terminal domain enabling protein dimerization. The H199 histidine is located on the PRD1 domain surface next to DNA-binding domains. The phosphorylation of H199 histidine will presumably change the domains interaction and their relative position in similar way to LicT protein, a PRD-containing anti-terminator protein. This conformational change can facilitate DNA binding. The second histidine undergoing phosphorylation, H379, is located on the PRD2 domain next to the dimerization interface. The His379 phosphorylation impairs AtxA dimers, the protein’s active form, as was deduced from the structure and confirmed by biological experiments.
The crystal structure of AtxA is the first reported structure of a PRD-containing virulence regulator. This structure can serve as a model for proteins of this family especially those that link virulence to bacterial metabolism.