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bioRxiv · 10.1101/721969

Translocational unfolding in clostridial binary iota toxin complex

Yamada, T.·Yoshida, T.·Kawamoto, A.·Mitsuka, K.·Iwasaki, K.·Tsuge, H.
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Abstract

Protein 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 {phi}-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 -helix tilting and partial unfolding, whereupon the unfolded N-terminus continues to the {phi}-clamp gate. This study reveals the novel mechanism of N-terminal unfolding, which is crucial for protein translocation.

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Yamada, T., Yoshida, T., Kawamoto, A., Mitsuka, K., Iwasaki, K., Tsuge, H.. 2019-08-01. Translocational unfolding in clostridial binary iota toxin complex. https://doi.org/10.1101/721969

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