par Jurenas, Dukas 
Président du jury Vanhamme, Luc
Promoteur Van Melderen, Laurence;Sužiedeliene, Edita
Co-Promoteur Garcia-Pino, Abel
Publication Non publié, 2018-12-06
Président du jury Vanhamme, Luc
Promoteur Van Melderen, Laurence
;Sužiedeliene, EditaCo-Promoteur Garcia-Pino, Abel
Publication Non publié, 2018-12-06
Thèse de doctorat
| Résumé : | Bacterial toxin-antitoxin (TA) systems are small genetic elements that are composed of a toxic protein and its cognate antidote that is unstable. Type II TA systems are the most common in bacterial genomes. In type II TAs both toxin and antitoxin are proteins that form a complex in which the toxic activity is inhibited. This complex also participates in transcription repression of the operon coding for TA. Even though these systems are abundant in bacterial genomes, their roles remain unclear. TAs encoded on mobile genetic elements contribute to their stability in growing population and favour their horizontal transfer. The function of TAs encoded on chromosomes is less clear and is a subject of intense debates. The predominant hypothesis is that they participate in stress response. The type II toxin are mostly translation inhibitors that target translation at different stages using different enzymatic activities. Some other type II toxins target DNA replication or synthesis of peptidoglycan. This thesis presents a novel toxin, AtaT, that modifies the initiator transfer RNA on the methionine. After the modification acetylated acMet-tRNAfMet fails to interact with initiation factor 2 and therefore is not delivered to the ribosome 30S subunit, which leads to translation inhibition. Crystal structures of AtaT toxin, its antitoxin AtaR and their complex interacting with DNA allow us to visualise the regulation cycle of AtaRT toxin antitoxin system. The link between the synthesis of the toxin, its neutralisation by the antitoxin and their participation in the transcription regulation of ataRT operon is validated both in vitro and in vivo. |
