Inhibition of translation termination by the antimicrobial peptide Drosocin.
Journal
Nature chemical biology
ISSN: 1552-4469
Titre abrégé: Nat Chem Biol
Pays: United States
ID NLM: 101231976
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
06
10
2022
accepted:
24
02
2023
medline:
28
8
2023
pubmed:
31
3
2023
entrez:
30
3
2023
Statut:
ppublish
Résumé
The proline-rich antimicrobial peptide (PrAMP) Drosocin (Dro) from fruit flies shows sequence similarity to other PrAMPs that bind to the ribosome and inhibit protein synthesis by varying mechanisms. The target and mechanism of action of Dro, however, remain unknown. Here we show that Dro arrests ribosomes at stop codons, probably sequestering class 1 release factors associated with the ribosome. This mode of action is comparable to that of apidaecin (Api) from honeybees, making Dro the second member of the type II PrAMP class. Nonetheless, analysis of a comprehensive library of endogenously expressed Dro mutants shows that the interactions of Dro and Api with the target are markedly distinct. While only a few C-terminal amino acids of Api are critical for binding, the interaction of Dro with the ribosome relies on multiple amino acid residues distributed throughout the PrAMP. Single-residue substitutions can substantially enhance the on-target activity of Dro.
Identifiants
pubmed: 36997647
doi: 10.1038/s41589-023-01300-x
pii: 10.1038/s41589-023-01300-x
doi:
Substances chimiques
Antimicrobial Peptides
0
drosocin
149924-99-2
Glycopeptides
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1082-1090Subventions
Organisme : NIAID NIH HHS
ID : R01 AI162961
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
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