AtxA, a Global Virulence Regulator From Bacillus anthracis

The Bacillus anthracis virulence regulator AtxA is a master regulator that 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 amino acids known as histidines: H199 and H379.

Researchers from the Center for Structural Genomics of Infectious Diseases, in collaboration with Dr. Theresa M. Koehler from the University of Texas at Houston, characterized the AtxA protein from B. anthracis. The AtxA crystal structure is multimodular with five distinct domains: two N-terminal DNA-binding domains, two phosphoenolpyruvate phosphotransferase system regulation domains (PRDs) 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 is expected to 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.





Crystal structure of Bacillus anthracis virulence regulator AtxA

Crystal structure of Bacillus anthracis virulence regulator AtxA

Crystal structure of Bacillus anthracis virulence regulator AtxA

Reference

Hammerstrom TG, Horton LB, Swick MC, Joachimiak A, Osipiuk J, Koehler TM. Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity. Mol Microbiol. 2014 Nov 17. [Epub ahead of print] PMID: 25402841. PDB entry: 4R6I. ​​

All featured structures from the NIAID Structural Genomics Centers​​​

 

Content last reviewed on