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Dual regulation of HEPN RNase in fused MNT-HEPN toxin-antitoxin systems via protein OligoAMPylation and oligomerization - PubMed

6 hours ago
  • #oligoAMPylation
  • #HEPN RNase
  • #toxin-antitoxin systems
  • HEPN domain-containing proteins have a conserved RNase motif and are found in both prokaryotes and eukaryotes.
  • Prokaryotic HEPN domain toxins often pair with MNT domain antitoxins to form type VII HepT/MntA toxin-antitoxin (TA) systems.
  • Fused MNT-HEPN proteins (FhepTA) in Shewanella genus resemble HepT/MntA TA systems and are carried by mobile genetic elements.
  • MntA antitoxin oligoAMPylates HepT toxin to block its toxicity when encoded as separate genes.
  • FhepTA toxicity is regulated by oligoAMPylation and a redox switch involving two unique cysteines in its HEPN domain.
  • The N-terminal MNT domain in FhepTA inhibits toxicity by preventing dimerization of the C-terminal HEPN domain.
  • Fused MNT-HEPN architecture represents a new family of TA modules regulated by ATP-dependent oligoAMPylation and redox-state-dependent oligomerization.