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TitleFlipping antimicrobial peptides in the exit tunnel of the bacterial ribosome.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJun 3, 2026
AuthorsWeiping Huang / Max J Berger / Haaris A Safdari / Dorota Klepacki / Helge Paternoga / Chetana Baliga / Daniel N Wilson / Nora Vázquez-Laslop / Alexander S Mankin /
PubMed AbstractProline-rich antimicrobial peptides (PrAMPs) kill bacteria by binding in the ribosomal nascent peptide exit tunnel. Type II PrAMPs bind in an orientation matching that of the nascent protein, trap ...Proline-rich antimicrobial peptides (PrAMPs) kill bacteria by binding in the ribosomal nascent peptide exit tunnel. Type II PrAMPs bind in an orientation matching that of the nascent protein, trap the release factors and arrest ribosomes at stop codons. Conversely, Type I PrAMPs bind in an opposite orientation: their N-terminus invades the peptidyl transferase center arresting translation at start codons. Here, by mining the genome databases, we identify a number of PrAMPs with high sequence similarity to the Type II PrAMP Drosocin. Notably, many of the new PrAMPs do not stall ribosomes at stop codons, but act as Type I PrAMPs arresting translation at start codons. Structural analysis shows that such peptides bind with a Type I orientation. Minimal alterations in the peptide structure can flip the orientation of the PrAMP in the exit tunnel, switching the mechanism of translation inhibition. Altering the mode of binding and action of a PrAMP by only few mutations could be exploited by the host to combat newly emerging bacterial pathogens.
External linksNat Commun / PubMed:42236475 / PubMed Central
MethodsEM (single particle)
Resolution2.54 - 3.11 Å
Structure data

EMDB-55844, PDB-9tew:
DalDro bound to the initiating Escherichia coli 70S ribosome
Method: EM (single particle) / Resolution: 2.9 Å

EMDB-55845, PDB-9tex:
Dal2 bound to the Escherichia coli 70S ribosome
Method: EM (single particle) / Resolution: 2.54 Å

EMDB-55847, PDB-9tey:
DalDro bound to the terminating Escherichia coli 70S ribosome
Method: EM (single particle) / Resolution: 3.11 Å

EMDB-55849, PDB-9tez:
DalDroS bound to the Escherichia coli 50S ribosomal subunit
Method: EM (single particle) / Resolution: 2.88 Å

Chemicals

ChemComp-ZN:
Unknown entry

ChemComp-SPM:
SPERMINE

ChemComp-HOH:
WATER

ChemComp-MG:
Unknown entry

Source
  • escherichia coli bw25113 (bacteria)
  • drosophila (fruit flies)
  • drosophila albomicans (fry)
KeywordsANTIBIOTIC / DalDro / Dal2 / Drosocin / PrAMP / Translation / Inhibitor / Initiation / NCPET / Ribosome / Cryo-EM / Termination / DalDroS

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