Dynamic gating by ϕ-clamp loop controls peptide translocation through the anthrax toxin nanopore.

ABSTRACT: The ϕ clamp, a key active site in the anthrax toxin protective antigen (PA) nanopore, governs the complex process of peptide translocation, yet its precise mechanism remains debated. A key question is how might the nanopore mitigate the formation of too stable/static of a ϕ-clamp interaction with the polymer it is attempting to translocate. One hypothesis is that it would "gate" to bind and "ungate" to release. Here, we dissect this mechanism using single-channel electrophysiology on wild-type PA and two ϕ-clamp mutants (F427A and F427Y). Thermodynamic analysis reveals the wild-type F427 residue creates a deep, energetically stable "hydrophobic trap" (state 0). Kinetic analysis further establishes F427 as a "specific chemical sensor"; the strong correlations between translocation kinetics

SUBMITTER: Colby JM 

PROVIDER: S-EPMC12834330 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature