Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes
Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes
Abstract Cells adjust to nutrient deprivation by reversible translational shut down. This is accompanied by maintaining inactive ribosomes in a hibernation state, where they are bound by proteins with inhibitory and protective functions. In eukaryotes, such a function was attributed to Stm1 (SERBP1 in mammals), and recently Lso2 (CCDC124 in mammals) was found to be involved in translational recovery after starvation from stationary phase. Here, we present cryo-electron microscopy (cryo-EM) structures of translationally inactive yeast and human ribosomes. We found Lso2/CCDC124 accumulating on idle ribosomes in the non-unrotated state, in contrast to Stm1/SERBP1-bound ribosomes, which display a rotated state. Lso2/CCDC124 bridges the decoding sites of the small with the GTPase-activating center of the large subunit. This position allows accommodation of the Dom34-dependent ribosome recycling system, which splits Lso2-containing but not Stm1-containing ribosomes. We propose a model in which Lso2 facilitates rapid translation reactivation by stabilizing the recycling-competent state of inactive ribosomes.
Wells Jennifer N.、Buschauer Robert、Mackens-Kiani Timur、Best Katharina、Gilbert Wendy、Kratzat Hanna、Berninghausen Otto、Beckmann Roland、Cheng Jingdong、Becker Thomas
Gene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichDepartment of Molecular Biophysics and Biochemistry, Yale UniversityGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of MunichGene Center and Center for Integrated Protein Science Munich, Department of Biochemistry, Feodor-Lynen-Str. 25, University of Munich
分子生物学细胞生物学生物化学
Wells Jennifer N.,Buschauer Robert,Mackens-Kiani Timur,Best Katharina,Gilbert Wendy,Kratzat Hanna,Berninghausen Otto,Beckmann Roland,Cheng Jingdong,Becker Thomas.Structure and function of yeast Lso2 and human CCDC124 bound to hibernating ribosomes[EB/OL].(2025-03-28)[2025-05-01].https://www.biorxiv.org/content/10.1101/2020.02.12.944066.点此复制
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