Genome-wide effects of the antimicrobial peptide apidaecin on translation termination in bacteria.
Genome-wide effects of the antimicrobial peptide apidaecin on translation termination in bacteria.
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DOI：
10.7554/elife.62655
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发表时间：
2020-10-08
期刊：
影响因子：
7.7
通讯作者：
Vázquez-Laslop N
中科院分区：
文献类型：
--
作者：
Mangano K;Florin T;Shao X;Klepacki D;Chelysheva I;Ignatova Z;Gao Y;Mankin AS;Vázquez-Laslop N
生物化学研究表明，抗微生物肽apidaecin（API）抑制蛋白质合成的结合在新生肽出口隧道和捕获释放因子与终止核糖体。API在细菌细胞中的作用方式仍然未知。全基因组分析显示，在细菌中，API在终止密码子处阻止翻译核糖体，并导致尾随核糖体的明显排队。通过隔离可用的释放因子，API促进普遍的终止密码子旁路，导致具有C-末端延伸的蛋白质的表达。Api介导的翻译停滞导致核糖体拯救系统的无效激活。了解API在活细胞中作用的独特机制可能有助于开发用于基因组探索的新药和研究工具。
Biochemical studies suggested that the antimicrobial peptide apidaecin (Api) inhibits protein synthesis by binding in the nascent peptide exit tunnel and trapping the release factor associated with a terminating ribosome. The mode of Api action in bacterial cells had remained unknown. Here genome-wide analysis reveals that in bacteria, Api arrests translating ribosomes at stop codons and causes pronounced queuing of the trailing ribosomes. By sequestering the available release factors, Api promotes pervasive stop codon bypass, leading to the expression of proteins with C-terminal extensions. Api-mediated translation arrest leads to the futile activation of the ribosome rescue systems. Understanding the unique mechanism of Api action in living cells may facilitate the development of new medicines and research tools for genome exploration.