par El Khalfaoui Oulali, Brahim 
Président du jury Van Melderen, Laurence
Promoteur Garcia-Pino, Abel
Publication Non publié, 2024-06-24
Président du jury Van Melderen, Laurence
Promoteur Garcia-Pino, Abel
Publication Non publié, 2024-06-24
Mémoire
| Résumé : | Toxin-antitoxin systems (TA systems) are genetic systems encoding at least two molecules: a toxin, which is a protein with a toxic activity, and an antitoxin, which can be a protein or a non-coding RNA. The antitoxin, typically less stable, neutralizes the toxic effect of the toxin, but it must be continuously produced. The CapRel-PanA TA system found in Vibrio harveyi has been shown to function as a defense system against bacteriophages, through a mechanism of abortive infection. VhCapRel is a fused TA system, meaning that the toxin and the antitoxin open reading frames (ORF) have fused together into a single ORF. The toxin domain catalyzes the reaction of tRNA pyrophosphorylation, leading to translation arrest. The antitoxin domain (a pseudo-Zn2+ finger domain) has been previously shown to neutralize the toxin domain in a homologous fused TA system (CapRel SJ46). VhPanA is a separate antitoxin that must be co-expressed for toxin neutralization. To understand the neutralization mechanism, I used the AlphaFold structural prediction of the VhCapRel-VhPanA complex (supported by SAXS data) to put forward a model, and I challenged the model with a functional assay in-vivo using mutants of VhCapRel. |
