MenT nucleotidyltransferase toxins extend tRNA acceptor stems and can be inhibited by asymmetrical antitoxin binding.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
17 08 2023
17 08 2023
Historique:
received:
28
02
2023
accepted:
20
07
2023
medline:
21
8
2023
pubmed:
18
8
2023
entrez:
17
8
2023
Statut:
epublish
Résumé
Mycobacterium tuberculosis, the bacterium responsible for human tuberculosis, has a genome encoding a remarkably high number of toxin-antitoxin systems of largely unknown function. We have recently shown that the M. tuberculosis genome encodes four of a widespread, MenAT family of nucleotidyltransferase toxin-antitoxin systems. In this study we characterize MenAT1, using tRNA sequencing to demonstrate MenT1 tRNA modification activity. MenT1 activity is blocked by MenA1, a short protein antitoxin unrelated to the MenA3 kinase. X-ray crystallographic analysis shows blockage of the conserved MenT fold by asymmetric binding of MenA1 across two MenT1 protomers, forming a heterotrimeric toxin-antitoxin complex. Finally, we also demonstrate tRNA modification by toxin MenT4, indicating conserved activity across the MenT family. Our study highlights variation in tRNA target preferences by MenT toxins, selective use of nucleotide substrates, and diverse modes of MenA antitoxin activity.
Identifiants
pubmed: 37591829
doi: 10.1038/s41467-023-40264-3
pii: 10.1038/s41467-023-40264-3
pmc: PMC10435456
doi:
Substances chimiques
Antitoxins
0
Nucleotidyltransferases
EC 2.7.7.-
Toxins, Biological
0
Nucleotides
0
RNA, Transfer
9014-25-9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4644Informations de copyright
© 2023. The Author(s).
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