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

Christos Gatsogiannis, Felipe Merino, Daniel Roderer, David Balchin, Evelyn Schubert, Anne Kuhlee, Manajit Hayer-Hartl and Stefan Raunser ()
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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

Nature, 2018, vol. 563, issue 7730, 209-213

Abstract: 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.

Keywords: Translocation Channel; Constriction Site; Toxic Enzymes; Molecular Dynamics Flexible Fitting (MDFF); Holotoxin (search for similar items in EconPapers)
Date: 2018
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DOI: 10.1038/s41586-018-0556-6

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