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| Title | Translation dynamics in human cells visualized at high resolution reveal cancer drug action. |
|---|---|
| Journal, issue, pages | Science, Vol. 381, Issue 6653, Page 70-75, Year 2023 |
| Publish date | Jul 7, 2023 |
 Authors | Huaipeng Xing / Reiya Taniguchi / Iskander Khusainov / Jan Philipp Kreysing / Sonja Welsch / Beata Turoňová / Martin Beck /  |
| PubMed Abstract | 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 ...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. |
 External links | Science / PubMed:37410833 |
| Methods | EM (subtomogram averaging) |
| Resolution | 3.1 - 18.1 Å |
| Structure data |  EMDB-16721: Human 80S ribosome in untreated cells  EMDB-16722: Human 80S ribosome in HHT-treated cells  EMDB-16725: Human 80S ribosome at the 'eEF1A, A/T, P' state in cells  EMDB-16726: Human 80S ribosome at the 'A/T, P' state in untreated cells  EMDB-16727: Human 80S ribosome at the 'eEF2, ap/P, pe/E' state in untreated cells  EMDB-16728: Human 80S ribosome at the 'eEF1A, A/T, P, E' state in untreated cells  EMDB-16733: Human 80S ribosome at the 'eEF2' state in untreated cells  EMDB-16734: Human 80S ribosome at the 'P' state in untreated cells  EMDB-16735: Human 80S ribosome at the 'A, P' state in untreated cells  EMDB-16736: Human 80S ribosome at the 'eEF1A, A/T, P, Z' state in untreated cells  EMDB-16737: Human di-ribosome in untreated cells  EMDB-16738: Human 80S ribosome with ES27L at conformation 1 in untreated cells  EMDB-16739: Human 80S ribosome with ES27L at conformation 2 in untreated cells  EMDB-16740: Human 80S ribosome with ES27L at conformation 3 in untreated cells  EMDB-16741: Human 80S ribosome with ES27L at conformation 4 in untreated cells  EMDB-16742: Human 80S ribosome with ES27L at conformation 5 in untreated cells  EMDB-16743: Human 60S in the cytoplasm of untreated cells  EMDB-16744: Human 80S ribosome at the 'eEF2' state in HHT-treated cells  EMDB-16747: Human 80S ribosome at the 'A, P' state in HHT-treated cells  EMDB-16748: Human 80S ribosome at the 'P' state in HHT-treated cells  EMDB-16749: Human 80S ribosome at the 'eEF1A, A/T, P, Z' state in HHT-treated cells  EMDB-16750: Human 80S ribosome at the 'A/T, P, Z' state in HHT-treated cells  EMDB-16751: Human 80S ribosome at the potential 'Compact eEF2, A, P' state in HHT-treated cells  EMDB-16752: Human 80S ribosome with ES27L at conformation 1 in HHT-treated cells  EMDB-16754: Human 80S ribosome with ES27L at conformation 5 in HHT-treated cells  EMDB-16755: Human 80S ribosome with ES27L at conformation 6 in HHT-treated cells  EMDB-16756: Human 80S ribosome with ES27L at conformation 7 in HHT-treated cells  EMDB-16757: Human 60S associated with eIF6 in the cytoplasm of HHT-treated cells |
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Homo sapiens (human)
Homo (humans)