Structural analysis of pathogenic proteins of B. anthracis and their interaction with human proteins

Abstract

Anthrax pathogenic proteins, including Protective Antigen (PA), Lethal Factor (LF), and Edema Factor (EF), are central to the virulence of Bacillus anthracis, presenting a significant threat to public health and national security. This study provides a comprehensive structural analysis of these proteins and their interactions with human proteins, such as CMG2, MEK, and calmodulin. Key structural features identified include PA's four domains: the N-terminal domain with the Furin protease cleavage site, the heptamerization domain, the pore-forming domains, and the receptor-binding domain with two critical loops. The analysis revealed critical interactions, such as PA D683 with CMG2 residues E117, S52, S54, and T118; LF residues K377, S331, and Q383 with MEK residues P10 and R4; and EF residues K505, K525, and S660 with calmodulin. These interactions are stabilized by hydrogen bonds, electrostatic forces and hydrophobic interactions, which are essential for the stability and function of the toxin-host complexes. The study underscores the significance of these interactions in facilitating the binding, internalization, and toxic effects of the anthrax toxins within human cells. Understanding the structural features and interactions of anthrax pathogenic proteins provides valuable insights into the molecular mechanisms underlying anthrax toxicity.