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.
Item Type: | Journal article |
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Faculties: | Chemistry and Pharmacy > Department of Biochemistry |
Research Centers: | Center for Integrated Protein Science Munich (CIPSM) |
Subjects: | 500 Science > 540 Chemistry |
ISSN: | 1545-9993 |
Language: | English |
Item ID: | 54083 |
Date Deposited: | 14. Jun 2018, 09:55 |
Last Modified: | 04. Nov 2020, 13:33 |