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Cell Rep. 2015 Sep 1;12(9):1497-507. doi: 10.1016/j.celrep.2015.07.056. Epub 2015 Aug 20.

Adenylylation of Gyrase and Topo IV by FicT Toxins Disrupts Bacterial DNA Topology.

Author information

1
Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland.
2
Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland; Focal Area Structural Biology and Biophysics, Biozentrum, University of Basel, 4056 Basel, Switzerland.
3
Centre for Cell and Molecular Biosciences, Newcastle University, NE2 4AX Newcastle upon Tyne, UK.
4
Proteomics Core Facility, Biozentrum, University of Basel, 4056 Basel, Switzerland.
5
Centre for Cell and Molecular Biosciences, Newcastle University, NE2 4AX Newcastle upon Tyne, UK; Department of Biology, University of Copenhagen, 2200 Copenhagen, Denmark.
6
Focal Area Structural Biology and Biophysics, Biozentrum, University of Basel, 4056 Basel, Switzerland.
7
Focal Area Infection Biology, Biozentrum, University of Basel, 4056 Basel, Switzerland. Electronic address: christoph.dehio@unibas.ch.

Abstract

Toxin-antitoxin (TA) modules are ubiquitous molecular switches controlling bacterial growth via the release of toxins that inhibit cell proliferation. Most of these toxins interfere with protein translation, but a growing variety of other mechanisms hints at a diversity that is not yet fully appreciated. Here, we characterize a group of FIC domain proteins as toxins of the conserved and abundant FicTA family of TA modules, and we reveal that they act by suspending control of cellular DNA topology. We show that FicTs are enzymes that adenylylate DNA gyrase and topoisomerase IV, the essential bacterial type IIA topoisomerases, at their ATP-binding site. This modification inactivates both targets by blocking their ATPase activity, and, consequently, causes reversible growth arrest due to the knotting, catenation, and relaxation of cellular DNA. Our results give insight into the regulation of DNA topology and highlight the remarkable plasticity of FIC domain proteins.

PMID:
26299961
DOI:
10.1016/j.celrep.2015.07.056
[Indexed for MEDLINE]
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