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

Florin, Tanja; Maracci, Cristina; Graf, Michael; Karki, Prajwal; Klepacki, Dorota; Berninghausen, Otto; Beckmann, Roland; Vazquez-Laslop, Nora; Wilson, Daniel N.; Rodnina, Marina V. und Mankin, Alexander S. (2017): An antimicrobial peptide that inhibits translation by trapping release factors on the ribosome. In: Nature Structural & Molecular Biology, Bd. 24, Nr. 9: S. 752-757

Abstract

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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Chemie und Pharmazie > Department Biochemie
• Fakultätsübergreifende Einrichtungen: Center for Integrated Protein Science Munich (CIPSM)
• Themengebiete: 500 Naturwissenschaften und Mathematik > 540 Chemie
• ISSN: 1545-9993
• Sprache: Englisch