An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome

Nat Struct Mol Biol. 2017 Sep;24(9):752-757. doi: 10.1038/nsmb.3439. Epub 2017 Jul 24.


Many antibiotics stop bacterial growth by inhibiting different steps of protein synthesis. However, no specific inhibitors of translation termination are known. Proline-rich antimicrobial peptides, a component of the antibacterial defense system of multicellular organisms, interfere with bacterial growth by inhibiting translation. Here we show that Api137, a derivative of the insect-produced antimicrobial peptide apidaecin, arrests terminating ribosomes using a unique mechanism of action. Api137 binds to the Escherichia coli ribosome and traps release factor (RF) RF1 or RF2 subsequent to the release of the nascent polypeptide chain. A high-resolution cryo-EM structure of the ribosome complexed with RF1 and Api137 reveals the molecular interactions that lead to RF trapping. Api137-mediated depletion of the cellular pool of free release factors causes the majority of ribosomes to stall at stop codons before polypeptide release, thereby resulting in a global shutdown of translation termination.

MeSH terms

  • Anti-Infective Agents / pharmacology*
  • Antimicrobial Cationic Peptides / pharmacology*
  • Cryoelectron Microscopy
  • Escherichia coli / drug effects
  • Escherichia coli Proteins / metabolism*
  • Escherichia coli Proteins / ultrastructure
  • Models, Biological
  • Models, Molecular
  • Peptide Termination Factors / metabolism*
  • Peptide Termination Factors / ultrastructure
  • Protein Biosynthesis / drug effects*
  • Ribosomes / drug effects*
  • Ribosomes / ultrastructure


  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Escherichia coli Proteins
  • Peptide Termination Factors
  • prfA protein, E coli
  • prfB protein, E coli
  • apidaecin