Weiping Huang, Chetana Baliga, Elena V Aleksandrova, Gemma Atkinson, Yury S Polikanov, Nora Vázquez-Laslop, Alexander S Mankin
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引用次数: 0
Abstract
Apidaecin 1b (Api), the first characterized Type II Proline-rich antimicrobial peptide (PrAMP), is encoded in the honey bee genome. It inhibits bacterial growth by binding in the nascent peptide exit tunnel of the ribosome after the release of the completed protein and trapping the release factors. By genome mining, we have identified 71 PrAMPs encoded in insect genomes as pre-pro-polyproteins. Having chemically synthesized and tested the activity of 26 peptides, we demonstrate that despite significant sequence variation in the N-terminal sequence, the majority of the PrAMPs that retain the conserved C-terminal sequence of Api are able to trap the ribosome at the stop codons and induce stop codon readthrough-all hallmarks of Type II PrAMP mode of action. Some of the characterized PrAMPs exhibit superior antibacterial activity in comparison with Api. The newly solved crystallographic structures of the ribosome complexed with Api and with the more active peptide Fva1 from the stingless bee demonstrate the universal placement of the PrAMPs' C-terminal pharmacophore in the post-release ribosome despite variations in their N-terminal sequence.
Apidaecin 1b (Api)是蜜蜂基因组中编码的第一个富含脯氨酸的第二类抗菌肽(PrAMP)。它能在完成蛋白质释放后结合到核糖体的新生肽出口隧道中,并捕获释放因子,从而抑制细菌生长。通过基因组挖掘,我们发现了昆虫基因组中编码的 71 种前多聚蛋白 PrAMPs。通过化学合成和测试 26 种肽的活性,我们证明尽管 N 端序列存在显著差异,但保留 Api 保守 C 端序列的大多数 PrAMPs 都能在终止密码子处捕获核糖体并诱导终止密码子的读取--这些都是第二类 PrAMP 作用模式的标志。与 Api 相比,一些具有特征的 PrAMPs 表现出更强的抗菌活性。新近解决的与 Api 和来自无刺蜂的活性更强的多肽 Fva1 复合物的核糖体晶体结构表明,尽管 PrAMPs 的 N 端序列不同,但它们的 C 端药效团普遍位于释放后的核糖体中。
期刊介绍:
EMBO Reports is a scientific journal that specializes in publishing research articles in the fields of molecular biology, cell biology, and developmental biology. The journal is known for its commitment to publishing high-quality, impactful research that provides novel physiological and functional insights. These insights are expected to be supported by robust evidence, with independent lines of inquiry validating the findings.
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