@article{a79eb5d46b2441eba53dae932348ba7e,
title = "A new family of bacterial ribosome hibernation factors",
abstract = "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.",
author = "Karla Helena-Bueno and Rybak, {Mariia Yu} and Ekemezie, {Chinenye L} and Rudi Sullivan and Brown, {Charlotte R} and Charlotte Dingwall and Arnaud Basl{\'e} and Claudia Schneider and Connolly, {James P R} and Blaza, {James N} and B{\'a}lint Cs{\"o}rg{\H o} and Moynihan, {Patrick J} and Gagnon, {Matthieu G} and Hill, {Chris H} and Melnikov, {Sergey V}",
note = "We thank B. Javid, Z. Lightowlers, B. van der Berg and H. Murray for comments on the manuscript; J. Turkenburg and S. Hart for work supporting the York cryo-EM facility; and A. Kereszt for providing the conjugative strain E. coli BW29427. This work was financed by the Newcastle University NUORS 2021 Award (to K.H.-B.), the James W. McLaughlin Fellowship Fund (to M.Yu.R.), the Medical Research Council (MR/N013840/1 to C.L.E.), the Biotechnology and Biological Sciences Research Council UK (BB/T008695/1 to C.R.B.), a UKRI Future Leader Fellowship (MR/T040742/1 to J.N.B.), the Lend{\"u}let (Momentum) Program of the Hungarian Academy of Sciences (LP2022-4/2022a to B.C.), a National Institutes of Health grant (R01GM136936 to M.G.G.), a Welch Foundation grant (H-2032-20230405 to M.G.G.), a Wellcome Trust & Royal Society Sir Henry Dale Fellowship (221818/Z/20/Z to C.H.H.) and the Royal Society (RGS/R2/202003 to S.V.M.). This project was undertaken on the NSBL Cluster and the Viking Cluster, which are high-performance compute facilities provided by Newcastle University and the University of York, respectively. We are grateful for computational support from the University of York High Performance Computing service, Viking and the Research Computing team, and support from the Newcastle University Structural Biology Laboratory. We also acknowledge the York cryo-EM facility supported by the Wellcome Trust (206161/Z/17/Z) and the York Centre of Excellence in Mass Spectrometry that was created with a capital investment through Science City York and supported by the Engineering and Physical Sciences Research Council (EP/K039660/1; EP/M028127/1) and Yorkshire Forward with funds from the Northern Way Initiative. We also acknowledge Diamond UK for access to and support of the cryo-EM facilities at the UK national electron Bio-Imaging Centre, proposal BI28576, financed by the Wellcome Trust, the Medical Research Council and the Biotechnology and Biological Sciences Research Council. We are grateful to M. Sherman for advice and support; K.-Y. Wong and J. Perkyns for computational support; and to the Sealy and Smith Foundation for supporting the Sealy Center for Structural Biology at the University of Texas Medical Branch. For the purpose of open access, the authors have applied a CC BY public copyright license to any author accepted manuscript version arising from this submission.",
year = "2024",
month = feb,
day = "14",
doi = "10.1038/s41586-024-07041-8",
language = "English",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
}