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

Nature
Christos GatsogiannisStefan Raunser

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.

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Citations

Nov 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Daniel RodererStefan Raunser
Oct 31, 2019·Science Advances·F LeidreiterS Raunser
Oct 5, 2019·Nature Structural & Molecular Biology·Christos GatsogiannisStefan Raunser
May 30, 2019·Annual Review of Microbiology·Daniel Roderer, Stefan Raunser
Apr 2, 2019·Frontiers in Neuroscience·Verity A JacksonElena Seiradake
Sep 22, 2019·Life Science Alliance·Peter Njenga Ng Ang AGudula Schmidt
Jun 3, 2020·Nature Communications·Daniel RodererStefan Raunser
May 18, 2019·IUCrJ·Yoshikazu TanakaChristos Gatsogiannis
Mar 27, 2020·Microbiology·David J Clarke
Nov 22, 2019·Nature Communications·Daniel RodererStefan Raunser
Jan 6, 2022·PLoS Pathogens·Patrick GüntherStefan Raunser

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Methods Mentioned

BETA
electron
biosensors

Software Mentioned

NAMD
PISA
Sc
PHENIX
PHASER
ConSurf Chimera
Rosetta
MODELLER
Clustal Omega
Chimera

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