A new family of bacterial ribosome hibernation factors
A new family of bacterial ribosome hibernation factors
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DOI：
10.1038/s41586-024-07041-8
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发表时间：
2024-02-29
期刊：
影响因子：
64.8
通讯作者：
Melnikov，Sergey V.
中科院分区：
文献类型：
--
作者：
Helena-Bueno，Karla;Rybak，Mariia Yu.;Melnikov，Sergey V.
为了在饥饿和应激时保存能量，许多生物利用冬眠因子蛋白来抑制蛋白质合成并保护其核糖体免受损伤。在细菌中，已经描述了两个冬眠因子家族，但是这些蛋白质的低保守性以及物种、栖息地和环境压力的巨大多样性使他们的发现变得混乱。在这里，通过结合低温电子显微镜，遗传学和生物化学，我们确定Balon，一个新的冬眠因子的冷适应细菌Psychrobacter urativorans。我们发现，Balon是一个遥远的同源物的古真核翻译因子aeRF 1，并发现在20%的代表性细菌。在冷休克或稳定期，Balon占据了核糖体A位点的空缺和积极翻译核糖体在复杂的EF-Tu，突出了意想不到的作用EF-Tu在细胞应激反应。与典型的A位点底物不同，Balon以不依赖于mRNA的方式与核糖体结合，启动了一种新的核糖体冬眠模式，这种模式可以在核糖体仍在进行蛋白质合成时开始。我们的工作表明，Balon-EF-Tu调节的核糖体冬眠是一种普遍存在的细菌应激反应机制，我们证明了分枝杆菌中假定的Balon同系物以类似的方式与核糖体结合。这一发现要求对从常见模式生物中推断出的核糖体冬眠的当前模型进行修订，并对我们如何理解和研究核糖体冬眠产生了许多影响。
To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage,. In bacteria, two families of hibernation factors have been described, but the low conservation of these proteins and the huge diversity of species, habitats and environmental stressors have confounded their discovery, , –. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacteriumPsychrobacter urativorans. We show that Balon is a distant homologue of the archaeo-eukaryotic translation factor aeRF1 and is found in 20% of representative bacteria. During cold shock or stationary phase, Balon occupies the ribosomal A site in both vacant and actively translating ribosomes in complex with EF-Tu, highlighting an unexpected role for EF-Tu in the cellular stress response. Unlike typical A-site substrates, Balon binds to ribosomes in an mRNA-independent manner, initiating a new mode of ribosome hibernation that can commence while ribosomes are still engaged in protein synthesis. Our work suggests that Balon–EF-Tu-regulated ribosome hibernation is a ubiquitous bacterial stress-response mechanism, and we demonstrate that putative Balon homologues inMycobacteriabind to ribosomes in a similar fashion. This finding calls for a revision of the current model of ribosome hibernation inferred from common model organisms and holds numerous implications for how we understand and study ribosome hibernation.