4R6I

AtxA protein, a virulence regulator from Bacillus anthracis.

Summary for 4R6I

• Entry DOI: 10.2210/pdb4r6i/pdb
• Descriptor: Anthrax toxin expression trans-acting positive regulator, DODECYL-BETA-D-MALTOSIDE (3 entities in total)
• Functional Keywords: structural genomics, idp01169, atxa, transcriptional activator, virulence regulator, dna binding, niaid, national institute of allergy and infectious diseases, center for structural genomics of infectious diseases, csgid, transcription
• Biological source: Bacillus anthracis (anthrax,anthrax bacterium)
• Total number of polymer chains: 2
• Total formula weight: 113677.05

Authors

Osipiuk, J.,Horton, L.B.,Koehler, T.M.,Anderson, W.F.,Joachimiak, A.,Center for Structural Genomics of Infectious Diseases (CSGID) (deposition date: 2014-08-25, release date: 2014-10-22, Last modification date: 2024-10-09)

Primary citation

Hammerstrom, T.G.,Horton, L.B.,Swick, M.C.,Joachimiak, A.,Osipiuk, J.,Koehler, T.M.
Crystal structure of Bacillus anthracis virulence regulator AtxA and effects of phosphorylated histidines on multimerization and activity.
Mol.Microbiol., 95:426-441, 2015

PubMed Abstract: The Bacillus anthracis virulence regulator AtxA controls transcription of the anthrax toxin genes and capsule biosynthetic operon. AtxA activity is elevated during growth in media containing glucose and CO(2)/bicarbonate, and there is a positive correlation between the CO(2)/bicarbonate signal, AtxA activity and homomultimerization. AtxA activity is also affected by phosphorylation at specific histidines. We show that AtxA crystallizes as a dimer. Distinct folds associated with predicted DNA-binding domains (HTH1 and HTH2) and phosphoenolpyruvate: carbohydrate phosphotransferase system-regulated domains (PRD1 and PRD2) are apparent. We tested AtxA variants containing single and double phosphomimetic (His→Asp) and phosphoablative (His→Ala) amino acid changes for activity in B. anthracis cultures and for protein-protein interactions in cell lysates. Reduced activity of AtxA H199A, lack of multimerization and activity of AtxAH379D variants, and predicted structural changes associated with phosphorylation support a model for control of AtxA function. We propose that (i) in the AtxA dimer, phosphorylation of H199 in PRD1 affects HTH2 positioning, influencing DNA-binding; and (ii) phosphorylation of H379 in PRD2 disrupts dimer formation. The AtxA structure is the first reported high-resolution full-length structure of a PRD-containing regulator, and can serve as a model for proteins of this family, especially those that link virulence to bacterial metabolism.

PubMed: 25402841
DOI: 10.1111/mmi.12867

Experimental method

X-RAY DIFFRACTION (2.65 Å)