Site-Specific Labeling and ¹⁹F NMR Provide Direct Evidence for Dynamic Behavior of the Anthrax Toxin Pore ϕ-Clamp Structure.

ABSTRACT: The anthrax toxin protective antigen (PA), the membrane binding and pore-forming component of the anthrax toxin, was studied using ¹⁹F NMR. We site-specifically labeled PA with p-fluorophenylalanine (pF-Phe) at Phe427, a critically important residue that comprises the ϕ-clamp that is required for translocation of edema factor (EF) and lethal factor (LF) into the host cell cytosol. We utilized ¹⁹F NMR to follow low-pH-induced structural changes in the prepore, alone and bound to the N-terminal PA binding domain of LF, LF_N. Our studies indicate that pF-Phe427 is dynamic in the prepore state and then becomes more dynamic in the transition to the pore. An increase in dynamic behavior at the ϕ-clamp may provide the necessary room for movement needed in translocating EF and LF into the cell cytosol.

SUBMITTER: Gonti S 

PROVIDER: S-EPMC8991541 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature