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Tc toxin activation requires unfolding and refolding of a β-propeller

Author

Listed:
  • Christos Gatsogiannis

    (Max Planck Institute of Molecular Physiology)

  • Felipe Merino

    (Max Planck Institute of Molecular Physiology)

  • Daniel Roderer

    (Max Planck Institute of Molecular Physiology)

  • David Balchin

    (Max Planck Institute of Biochemistry)

  • Evelyn Schubert

    (Max Planck Institute of Molecular Physiology)

  • Anne Kuhlee

    (Max Planck Institute of Molecular Physiology)

  • Manajit Hayer-Hartl

    (Max Planck Institute of Biochemistry)

  • Stefan Raunser

    (Max Planck Institute of Molecular Physiology)

Abstract

Tc toxins secrete toxic enzymes into host cells using a unique syringe-like injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA forms the translocation channel and the TcB–TcC heterodimer functions as a cocoon that shields the toxic enzyme. Binding of the cocoon to the channel triggers opening of the cocoon and translocation of the toxic enzyme into the channel. Here we show in atomic detail how the assembly of the three components activates the toxin. We find that part of the cocoon completely unfolds and refolds into an alternative conformation upon binding. The presence of the toxic enzyme inside the cocoon is essential for its subnanomolar binding affinity for the TcA subunit. The enzyme passes through a narrow negatively charged constriction site inside the cocoon, probably acting as an extruder that releases the unfolded protein with its C terminus first into the translocation channel.

Suggested Citation

  • Christos Gatsogiannis & Felipe Merino & Daniel Roderer & David Balchin & Evelyn Schubert & Anne Kuhlee & Manajit Hayer-Hartl & Stefan Raunser, 2018. "Tc toxin activation requires unfolding and refolding of a β-propeller," Nature, Nature, vol. 563(7730), pages 209-213, November.
    • Handle: RePEc:nat:nature:v:563:y:2018:i:7730:d:10.1038_s41586-018-0556-6
    DOI: 10.1038/s41586-018-0556-6
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    Cited by:

    1. Alexander Belyy & Philipp Heilen & Philine Hagel & Oliver Hofnagel & Stefan Raunser, 2023. "Structure and activation mechanism of the Makes caterpillars floppy 1 toxin," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    2. Shiheng Liu & Xian Xia & Eric Calvo & Z. Hong Zhou, 2023. "Native structure of mosquito salivary protein uncovers domains relevant to pathogen transmission," Nature Communications, Nature, vol. 14(1), pages 1-12, December.

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