EMD-43075
Cryo-EM structure of the Mycobacterium smegmatis 70S ribosome in complex with hibernation factor Rv2629 (Balon) (Structure 5)
EMD-43075
Single-particle3.1 Å
Deposition: 08/12/2023
Map released: 07/02/2024
Last modified: 13/03/2024
Sample Organism:
Mycolicibacterium smegmatis MC2 155,
Mycobacterium tuberculosis H37Rv
Sample: Cryo-EM structure of the Mycobacterium smegmatis 70S ribosome in complex with hibernation factor Rv2629 (Balon) (Structure 5)
Fitted models: 8v9k (Avg. Q-score: 0.461)
Deposition Authors: Rybak MY , Helena-Bueno K , Hill CH , Melnikov SV , Gagnon MG
Sample: Cryo-EM structure of the Mycobacterium smegmatis 70S ribosome in complex with hibernation factor Rv2629 (Balon) (Structure 5)
Fitted models: 8v9k (Avg. Q-score: 0.461)
Deposition Authors: Rybak MY , Helena-Bueno K , Hill CH , Melnikov SV , Gagnon MG
A new family of bacterial ribosome hibernation factors.
Helena-Bueno K ,
Rybak MY ,
Ekemezie CL ,
Sullivan R,
Brown CR ,
Dingwall C,
Basle A ,
Schneider C ,
Connolly JPR,
Blaza JN ,
Csorgo B ,
Moynihan PJ ,
Gagnon MG ,
Hill CH ,
Melnikov SV
(2024) Nature , 626 , 1125 - 1132
(2024) Nature , 626 , 1125 - 1132
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.
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.