[Detection of the functionally active domains in the molecule of protective antigen of the anthrax exotoxin]

Using the limited proteolysis method, we established that the protective antigen (PA) molecule consists of four functionally active domains. The shielding domain occupies an area in the linear structure of the molecule PA with NH4-terminal up to Lys166 and plays an important role in the proteolytic activation of PA. The associative domain situated in the Arg167-Met266 region is responsible for interactions with either lethal or edematous factors in self-assembly of the toxic complexes of the lethal or edematous toxin. The stabilizing domain occupies the Gly351 to Met434 area. On the one hand, this area promotes the formation of conformationally stable toxic complexes with the lethal factor, on the other, directly participates in the formation of the hydrophobic canal, through which the molecule of the lethal or edematous factor and, evidently, a fragment of PA molecule as well (from Arg167 to Gly314), including the associative gene, gets inside the target cell. The receptor domain representing a COOH-terminal region, starting from Leu663 amino acid, interacts with the specific receptors on macrophages and thus delivers the toxic complex to the target cell.