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Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile

Author

Listed:
  • Akihiro Kawamoto

    (Osaka University
    Japan Science and Technology Agency, PRESTO)

  • Tomohito Yamada

    (Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku)

  • Toru Yoshida

    (Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku
    Japan Women’s University)

  • Yusui Sato

    (Analytical Instruments R&D Division, HORIBA, Ltd.)

  • Takayuki Kato

    (Osaka University)

  • Hideaki Tsuge

    (Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku
    Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku
    Kyoto Sangyo University, Kamigamo-motoyama, Kita-ku)

Abstract

Some bacteria express a binary toxin translocation system, consisting of an enzymatic subunit and translocation pore, that delivers enzymes into host cells through endocytosis. The most clinically important bacterium with such a system is Clostridioides difficile (formerly Clostridium). The CDTa and CDTb proteins from its system represent important therapeutic targets. CDTb has been proposed to be a di-heptamer, but its physiological heptameric structure has not yet been reported. Here, we report the cryo-EM structure of CDTa bound to the CDTb-pore, which reveals that CDTa binding induces partial unfolding and tilting of the first CDTa α-helix. In the CDTb-pore, an NSS-loop exists in ‘in’ and ‘out’ conformations, suggesting its involvement in substrate translocation. Finally, 3D variability analysis revealed CDTa movements from a folded to an unfolded state. These dynamic structural information provide insights into drug design against hypervirulent C. difficile strains.

Suggested Citation

  • Akihiro Kawamoto & Tomohito Yamada & Toru Yoshida & Yusui Sato & Takayuki Kato & Hideaki Tsuge, 2022. "Cryo-EM structures of the translocational binary toxin complex CDTa-bound CDTb-pore from Clostridioides difficile," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33888-4
    DOI: 10.1038/s41467-022-33888-4
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    References listed on IDEAS

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    1. Jiansen Jiang & Bradley L. Pentelute & R. John Collier & Z. Hong Zhou, 2015. "Atomic structure of anthrax protective antigen pore elucidates toxin translocation," Nature, Nature, vol. 521(7553), pages 545-549, May.
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