Description
Prokaryotic toxin-antitoxin modules are involved in the establishment of persister cells. The latter involves complex regulatory mechanisms that link the regulation of protein activity to regulation of transcription. Recent structural and biochemical data shows a plethora of molecular mechanisms to achieve this goal. In the phd/doc module, conditional co-operativity is established via a combination of negative co-operativity through entropic exclusion of and IDP domain combined with a low to high affinity switch for the interaction between toxin and antitoxin. While Doc stabilizes the DNA binding conformation of Phd, Phd likewise inhibits the kinase activity of Doc and simultaneously prevents misfolding of Doc. The same phenomenon of conditional co-operativity is observed for mazEF and ccdAB, but with a different structural basis, although intrinsic disorder in the antitoxin is a common theme. Other TA modules such as higBA are regulated through a seemingly more simple mechanism where the antitoxin acts as the sole repressor, while toxin significantly weakens operator binding. Such a mechanism is observed in several higBA modules as well as in mqsRA and allows for transcription regulation without the specific need of intrinsic disorder.Period | 6 Jun 2015 → 11 Jun 2015 |
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Event title | 6th FEMS Congress of European Microbiologists |
Event type | Conference |
Location | Maastricht, Netherlands |
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Research output
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The Intrinsically Disordered Domain of the Antitoxin Phd Chaperones the Toxin Doc Against Irreversible Inactivation and Misfolding
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Computational Methods to Model Persistence
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A general model for toxin-antitoxin module dynamics can explain persister cell formation in E. coli.
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Energetic basis of uncoupling folding from binding for an intrinsically disordered protein
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Disorder- and Dynamics-Based Regulatory Mechanisms in Toxin-Antitoxin Modules.
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Crystallization of two operator complexes from the Vibrio cholerae higBA2 toxin-antitoxin module
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The Fic protein Doc uses an inverted substrate to phosphorylate and inactivate EF-Tu
Research output: Contribution to journal › Article › peer-review
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Small-Angle X-Ray Scattering- and Nuclear Magnetic Resonance-Derived Conformational Ensemble of the Highly Flexible Antitoxin PaaA2.
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The many faces of Fic: structural and functional aspects of Fic enzymes
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Structural and biophysical characterization of Staphylococcus aureus SaMazF shows conservation of functional dynamics.
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Allostery and intrinsic disorder mediate transcription regulation by conditional co-operativity
Research output: Contribution to journal › Article › peer-review
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An efficient method for the purification of proteins from four distinct toxin–antitoxin modules
Research output: Contribution to journal › Article › peer-review
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Projects
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Bacterial toxin-antitoxin modules as drug targets
Project: Fundamental
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Molecular mechanisms of intrinsically disordered proteins
Project: Fundamental
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New mechanisms of transcription regulation in prokaryotes
Project: Fundamental
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Regulatory mechanisms in bacterial toxin-antitoxin modules
Project: Fundamental