Mechanism of Gyrase-poisoning by ParE and its rejuvenation by ParD

Project Details

Description

In order to survive and thrive like any living organism, bacterial cells need to be able to adapt themselves to a changing environment. Toxin-antitoxin (TA) systems are small genetic elements that contribute to bacterial stress response: the pathway that tunes replication, transcription and translation to the environmental conditions including the availability of nutrients. They typically consist of two genes. The first one encodes a "toxin" that slows down or
halts basic cellular functions. The second one encodes a corresponding "antitoxin" that regulates the action of the toxin and protects against its potential lethal activity. TA systems are highly diverse, with many different unrelated families identified. Most often they target protein synthesis via various mechanisms, making them interesting for the development of novel antibiotics.
The parDE family of TA systems targets Gyrase by stabilizing a covalent DNA-Gyrase adduct that provides a roadblock for the transcription and replication machinery. Despite their abundance on bacterial chromosomes, the molecular details behind this Gyrase poisoning are not understood. With this project, I propose by a combination of structural biology and biophysical techniques to unravel how the toxin ParE2 from Vibrio cholerae inhibits Gyrase and how the corresponding antitoxin ParD2 can rescue the cells from ParE2-poisoned Gyrase .
AcronymFWOTM961
StatusFinished
Effective start/end date1/11/1931/01/24

Keywords

  • Protein science
  • Gyrase Poison

Flemish discipline codes in use since 2023

  • Structural biology
  • Molecular biophysics

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