Mechanisms of neutralization of toxSAS from toxin-antitoxin modules.
Nat Chem Biol
; 2024 Jun 04.
Article
de En
| MEDLINE
| ID: mdl-38834893
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Langue:
En
Journal:
Nat Chem Biol
/
Nat. chem. biol
/
Nature chemical biology
Sujet du journal:
BIOLOGIA
/
QUIMICA
Année:
2024
Type de document:
Article
Pays d'affiliation:
Belgique
Pays de publication:
États-Unis d'Amérique