Mechanism of Tc toxin action revealed in molecular detail

Dominic Meusch, Christos Gatsogiannis, Rouslan G. Efremov, Alexander E. Lang, Oliver Hofnagel, Ingrid R. Vetter, Klaus Aktories and Stefan Raunser ()
Additional contact information
Dominic Meusch: Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
Christos Gatsogiannis: Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
Rouslan G. Efremov: Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
Alexander E. Lang: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany
Oliver Hofnagel: Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
Ingrid R. Vetter: Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany
Klaus Aktories: Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Albert-Ludwigs-Universität Freiburg, 79104 Freiburg, Germany
Stefan Raunser: Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany

Nature, 2014, vol. 508, issue 7494, 61-65

Abstract: Abstract Tripartite Tc toxin complexes of bacterial pathogens perforate the host membrane and translocate toxic enzymes into the host cell, including in humans. The underlying mechanism is complex but poorly understood. Here we report the first, to our knowledge, high-resolution structures of a TcA subunit in its prepore and pore state and of a complete 1.7 megadalton Tc complex. The structures reveal that, in addition to a translocation channel, TcA forms four receptor-binding sites and a neuraminidase-like region, which are important for its host specificity. pH-induced opening of the shell releases an entropic spring that drives the injection of the TcA channel into the membrane. Binding of TcB/TcC to TcA opens a gate formed by a six-bladed β-propeller and results in a continuous protein translocation channel, whose architecture and properties suggest a novel mode of protein unfolding and translocation. Our results allow us to understand key steps of infections involving Tc toxins at the molecular level.

Date: 2014
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/nature13015 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:508:y:2014:i:7494:d:10.1038_nature13015

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature13015

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().