A new family of bacterial ribosome hibernation factors

TY - JOUR

T1 - A new family of bacterial ribosome hibernation factors

AU - Helena-Bueno, Karla

AU - Rybak, Mariia Yu

AU - Ekemezie, Chinenye L

AU - Sullivan, Rudi

AU - Brown, Charlotte R

AU - Dingwall, Charlotte

AU - Baslé, Arnaud

AU - Schneider, Claudia

AU - Connolly, James P R

AU - Blaza, James N

AU - Csörgő, Bálint

AU - Moynihan, Patrick J

AU - Gagnon, Matthieu G

AU - Hill, Chris H

AU - Melnikov, Sergey V

N1 - © 2024. The Author(s).

PY - 2024/2/29

Y1 - 2024/2/29

N2 - To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage 1,2. 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 discovery 3-6. 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.

AB - To conserve energy during starvation and stress, many organisms use hibernation factor proteins to inhibit protein synthesis and protect their ribosomes from damage 1,2. 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 discovery 3-6. 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.

KW - Ribosomal Proteins/genetics

KW - Peptide Elongation Factor Tu/metabolism

KW - Ribosomes/metabolism

KW - Protein Biosynthesis

KW - Bacteria/genetics

KW - Bacterial Proteins/metabolism

U2 - 10.1038/s41586-024-07041-8

DO - 10.1038/s41586-024-07041-8

M3 - Article

C2 - 38355796

SN - 0028-0836

VL - 626

SP - 1125

EP - 1132

JO - Nature

JF - Nature

IS - 8001

ER -