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Translation dynamics in human cells visualized at high resolution reveal cancer drug action

MPG-Autoren
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Xing,  Huaipeng       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;
Faculty of Biochemistry, Chemistry and Pharmacy, Goethe University Frankfurt am Main, Frankfurt am Main, Germany;

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Taniguchi,  Reiya       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

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Khusainov,  Iskander       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

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Kreysing,  Jan Philipp       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;
IMPRS-CBP, Max Planck Institute of Biophysics, Max Planck Society;

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Welsch,  Sonja       
Central Electron Microscopy Facility, Max Planck Institute of Biophysics, Max Planck Society;

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Turoňová,  Beata       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;

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Beck,  Martin       
Department of Molecular Sociology, Max Planck Institute of Biophysics, Max Planck Society;
Institute of Biochemistry, Goethe University Frankfurt, Frankfurt am Main, Germany;

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Zitation

Xing, H., Taniguchi, R., Khusainov, I., Kreysing, J. P., Welsch, S., Turoňová, B., et al. (2023). Translation dynamics in human cells visualized at high resolution reveal cancer drug action. Science, 381(6653), 70-75. doi:10.1126/science.adh1411.


Zitierlink: https://hdl.handle.net/21.11116/0000-000D-6B03-8
Zusammenfassung
Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, but their distribution in actively translating human cells remains elusive. We used a cryo-electron tomography-based approach and resolved ribosome structures inside human cells with high resolution. These structures revealed the distribution of functional states of the elongation cycle, a Z transfer RNA binding site, and the dynamics of ribosome expansion segments. Ribosome structures from cells treated with Homoharringtonine, a drug used against chronic myeloid leukemia, revealed how translation dynamics were altered in situ and resolve the small molecules within the active site of the ribosome. Thus, structural dynamics and drug effects can be assessed at high resolution within human cells.