A new family of bacterial ribosome hibernation factors

• 成果类型: Article
• 署名作者: Helena-Bueno, Karla; Rybak, Mariia Yu.; Ekemezie, Chinenye L.; Sullivan, Rudi; Brown, Charlotte R.; Dingwall, Charlotte; Basle, Arnaud; Schneider, Claudia; Connolly, James P. R.; Blaza, James N.; Csoergo, Balint; Moynihan, Patrick J.; Gagnon, Matthieu G.; Hill, Chris H.; Melnikov, Sergey V.
• 署名单位: Newcastle University - UK; University of Texas System; University of Texas Medical Branch Galveston; University of Birmingham; University of York - UK; University of York - UK; University of York - UK; HUN-REN; HUN-REN Biological Research Center; University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; University of Texas System; University of Texas Medical Branch Galveston; University of York - UK
• 刊物名称: Nature
• ISSN/ISSBN: 0028-6309
• DOI: 10.1038/s41586-024-07041-8
• 发表日期: 2024-02-29
• 关键词: peptide-bond formation; structural basis; crystal-structure; escherichia-coli; protein; elongation; termination; ef1-alpha; mechanism; database

摘要

To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage1,2. 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 discovery3-6. Here, by combining cryogenic electron microscopy, genetics and biochemistry, we identify Balon, a new hibernation factor in the cold-adapted bacterium Psychrobacter 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 in Mycobacteria bind 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. A study identifies a new bacterial ribosome hibernation factor, Balon, and describes its association with EF-Tu and its initiation of mRNA-independent hibernation during protein synthesis.