Translation dynamics in human cells visualized at high-resolution reveal cancer drug action
- Ribosomes catalyze protein synthesis by cycling through various functional states. These states have been extensively characterized in vitro, yet their distribution in actively translating human cells remains elusive. Here, we optimized a cryo-electron tomography-based approach and resolved ribosome structures inside human cells with a local resolution of up to 2.5 angstroms. These structures revealed the distribution of functional states of the elongation cycle, a Z tRNA binding site and the dynamics of ribosome expansion segments. In addition, we visualized structures of Homoharringtonine, a drug for chronic myeloid leukemia treatment, within the active site of the ribosome and found that its binding reshaped the landscape of translation. Overall, our work demonstrates that structural dynamics and drug effects can be assessed at near-atomic detail within human cells.
Download full text files
Additional Services
| Author: | Huaipeng XingORCiD, Reiya TaniguchiORCiD, Iskander KhusainovORCiD, Jan Philipp KreysingORCiD, Sonja WelschORCiDGND, Beata TuroňováORCiD, Martin BeckORCiDGND |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-723801 |
| DOI: | https://doi.org/10.1101/2023.03.02.529652 |
| Parent Title (English): | bioRxiv |
| Document Type: | Preprint |
| Language: | English |
| Date of Publication (online): | 2023/03/02 |
| Date of first Publication: | 2023/03/02 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2023/03/26 |
| Issue: | 2023.03.02.529652 |
| Page Number: | 23 |
| HeBIS-PPN: | 509805892 |
| Institutes: | Biochemie, Chemie und Pharmazie |
| Dewey Decimal Classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit | |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - CC BY-NC-ND - Namensnennung - Nicht kommerziell - Keine Bearbeitungen 4.0 International |
