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Ornithine capture by a translating ribosome controls bacterial polyamine synthesis.
Nature Microbiology ( IF 28.3 ) Pub Date : 2020-02-24 , DOI: 10.1038/s41564-020-0669-1
Alba Herrero Del Valle 1, 2, 3 , Britta Seip 1, 2, 3, 4 , Iñaki Cervera-Marzal 1, 2, 3, 5 , Guénaël Sacheau 1, 2, 3, 6 , A Carolin Seefeldt 1, 2, 3, 7 , C Axel Innis 1, 2, 3
Affiliation  

Polyamines are essential metabolites that play an important role in cell growth, stress adaptation and microbial virulence1,2,3. To survive and multiply within a human host, pathogenic bacteria adjust the expression and activity of polyamine biosynthetic enzymes in response to different environmental stresses and metabolic cues2. Here, we show that ornithine capture by the ribosome and the nascent peptide SpeFL controls polyamine synthesis in γ-proteobacteria by inducing the expression of the ornithine decarboxylase SpeF4, via a mechanism involving ribosome stalling and transcription antitermination. In addition, we present the cryogenic electron microscopy structure of an Escherichia coli ribosome stalled during translation of speFL in the presence of ornithine. The structure shows how the ribosome and the SpeFL sensor domain form a highly selective binding pocket that accommodates a single ornithine molecule but excludes near-cognate ligands. Ornithine pre-associates with the ribosome and is then held in place by the sensor domain, leading to the compaction of the SpeFL effector domain and blocking the action of release factor 1. Thus, our study not only reveals basic strategies by which nascent peptides assist the ribosome in detecting a specific metabolite, but also provides a framework for assessing how ornithine promotes virulence in several human pathogens.



中文翻译:

翻译核糖体捕获的鸟氨酸控制细菌多胺的合成。

多胺是必需的代谢物,在细胞生长、压力适应和微生物毒力1,2,3中发挥重要作用。为了在人类宿主中生存和繁殖,病原菌会根据不同的环境压力和代谢线索2调整多胺生物合成酶的表达和活性。在这里,我们表明核糖体和新生肽 SpeFL 捕获鸟氨酸通过诱导鸟氨酸脱羧酶 SpeF 4的表达,通过涉及核糖体停滞和转录抗终止的机制来控制 γ-变形菌中的多胺合成。此外,我们展示了在翻译过程中停滞的大肠杆菌核糖体的低温电子显微镜结构。speFL在存在鸟氨酸的情况下。该结构显示了核糖体和 SpeFL 传感器域如何形成一个高度选择性的结合口袋,该口袋可容纳单个鸟氨酸分子但不包括近同源配体。鸟氨酸与核糖体预结合,然后被传感器域保持在原位,导致 SpeFL 效应域的压缩并阻断释放因子 1 的作用。因此,我们的研究不仅揭示了新生肽辅助的基本策略核糖体检测特定代谢物,但也为评估鸟氨酸如何促进几种人类病原体的毒力提供了框架。

更新日期:2020-02-24
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