Abstract
AbstractProtein translocation across the membrane is critical for microbial pathogenesis and various cellular functions. Bacterial binary toxins such as anthrax toxin are composed of enzyme components and a translocation channel, which catalyses substrate unfolding and translocation. Here we report the structures of the clostridial binary toxin (iota toxin) translocation channel Ib-pore and its complex with ADP-ribosyltransferase Ia. The Ib-pore structure at atomic resolution provides a similar structural framework as observed for the catalytic ϕ-clamp of the anthrax protective antigen pore. However, the Ia-bound Ib-pore structure showed a unique binding mode of Ia: one Ia binds to the Ib-pore, and the Ia N-terminal domain interacts with Ib via two other Ib-pore bottlenecks with multiple weak interactions. Furthermore, Ib-binding induces Ia N-terminal α-helix tilting and partial unfolding, whereupon the unfolded N-terminus continues to the ϕ-clamp gate. This study reveals the novel mechanism of N-terminal unfolding, which is crucial for protein translocation.
Publisher
Cold Spring Harbor Laboratory