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.

中文翻译：

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通过捕获核糖体上的释放因子来抑制翻译的抗菌肽

许多抗生素通过抑制蛋白质合成的不同步骤来阻止细菌生长。但是，尚无翻译终止的特异性抑制剂。富含脯氨酸的抗菌肽是多细胞生物抗菌防御系统的组成部分，通过抑制翻译来干扰细菌的生长。在这里，我们显示Api137是昆虫产生的抗菌肽阿迪霉素的衍生物，它使用独特的作用机制来阻止终止的核糖体。Api137与大肠杆菌结合新生多肽链释放后，核糖体和陷阱释放因子（RF）RF1或RF2。与RF1和Api137复合的核糖体的高分辨率低温电磁结构揭示了导致RF捕获的分子相互作用。Api137介导的自由释放因子细胞池的耗竭会导致大多数核糖体在多肽释放之前停在终止密码子上，从而导致翻译终止的整体关闭。