par Dominguez Molina, Lucia 
;Kurata, Tatsuaki;Cepauskas, Albinas ;Echemendia Blanco, Dannele ;Zedek, Safia ;Talavera Perez, Ariel ;Atkinson, Gemma Catherine;Hauryliuk, Vasili;Garcia-Pino, Abel
Référence Nature Chemical Biology
Publication Publié, 2024-06
;Kurata, Tatsuaki;Cepauskas, Albinas ;Echemendia Blanco, Dannele ;Zedek, Safia ;Talavera Perez, Ariel ;Atkinson, Gemma Catherine;Hauryliuk, Vasili;Garcia-Pino, Abel Référence Nature Chemical Biology
Publication Publié, 2024-06
Article révisé par les pairs
| Résumé : | Toxic small alarmone synthetase (toxSAS) enzymes constitute a family of bacterial effectors present in toxin-antitoxin and secretion systems. toxSASs act through either translation inhibition mediated by pyrophosphorylation of transfer RNA (tRNA) CCA ends or synthesis of the toxic alarmone adenosine pentaphosphate ((pp)pApp) and adenosine triphosphate (ATP) depletion, exemplified by FaRel2 and FaRel, respectively. However, structural bases of toxSAS neutralization are missing. Here we show that the pseudo-Zn2+ finger domain (pZFD) of the ATfaRel2 antitoxin precludes access of ATP to the pyrophosphate donor site of the FaRel2 toxin, without affecting recruitment of the tRNA pyrophosphate acceptor. By contrast, (pp)pApp-producing toxSASs are inhibited by Tis1 antitoxin domains though occlusion of the pyrophosphate acceptor-binding site. Consequently, the auxiliary pZFD of AT2faRel is dispensable for FaRel neutralization. Collectively, our study establishes the general principles of toxSAS inhibition by structured antitoxin domains, with the control strategy directly coupled to toxSAS substrate specificity. |
