Ribosome hibernation is a commonly used strategy that protects ribosomes under unfavorable conditions and regulates developmental processes. Multiple ribosome-hibernation factors have been identified in all domains of life, but due to their structural diversity and the lack of a common inactivation mechanism, it is currently unknown how many different hibernation factors exist. Here, we show that the YqjD/ElaB/YgaM paralogs, initially discovered as membrane-bound ribosome binding proteins in E. coli, constitute an abundant class of ribosome-hibernating proteins, which are conserved across all proteobacteria and some other bacterial phyla. Our data demonstrate that they inhibit in vitro protein synthesis by interacting with the 50S ribosomal subunit. In vivo cross-linking combined with mass spectrometry revealed their specific interactions with proteins surrounding the ribosomal tunnel exit and even their penetration into the ribosomal tunnel. Thus, YqjD/ElaB/YgaM inhibit translation by blocking the ribosomal tunnel and thus mimic the activity of antimicrobial peptides and macrolide antibiotics.

中文翻译：

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一类广泛分布的 C 尾锚定膜蛋白的核糖体失活


核糖体冬眠是一种常用的策略，可在不利条件下保护核糖体并调节发育过程。在生命的所有领域中都已鉴定出多种核糖体冬眠因子，但由于它们的结构多样性和缺乏共同的失活机制，目前尚不清楚存在多少种不同的冬眠因子。在这里，我们表明 YqjD/ElaB/YgaM 旁系同源物最初在大肠杆菌中 作为膜结合核糖体结合蛋白被发现，构成了一类丰富的核糖体冬眠蛋白，它们在所有变形菌门和一些其他细菌门中都是保守的。我们的数据表明，它们通过与 50S 核糖体亚基相互作用来抑制 体外蛋白质合成。体内 交联结合质谱揭示了它们与核糖体隧道出口周围蛋白质的特异性相互作用，甚至它们渗透到核糖体隧道中。因此，YqjD/ElaB/YgaM 通过阻断核糖体隧道来抑制翻译，从而模拟抗菌肽和大环内酯类抗生素的活性。