A loop network within the anthrax toxin pore positions the phenylalanine clamp in an active conformation.

Heptameric pores formed in the endosomal membrane by the protective antigen moiety of anthrax toxin serve as portals for entry of the enzymatic moieties of the toxin into the cytosol. In the aqueous lumen of each pore is a "Phe clamp," a heptad of narrowly apposed Phe residues (Phe-427), that catalyzes the unfolding and translocation of the enzymatic moieties across the membrane. Here, we provide evidence for a "loop swap" between neighboring protective antigen subunits, which is required for efficient translocation and is mediated by a salt bridge formed between the side chains of Lys-397 and Asp-426. We propose that the interaction between residues 397 and 426 creates a structural framework that positions Phe-427 within the pore lumen, forming a functional Phe clamp and, hence, a translocation-competent pore.