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| Title | Visualizing the translation landscape in human cells at high resolution. |
|---|---|
| Journal, issue, pages | Nat Commun, Vol. 16, Issue 1, Page 10757, Year 2025 |
| Publish date | Nov 28, 2025 |
Authors | Wei Zheng / Yuekang Zhang / Jimin Wang / Shuhui Wang / Pengxin Chai / Elizabeth J Bailey / Chenghao Zhu / Wangbiao Guo / Swapnil C Devarkar / Shenping Wu / Jianfeng Lin / Kai Zhang / Jun Liu / Ivan B Lomakin / Yong Xiong / ![]() |
| PubMed Abstract | Comprehensive in situ structures of macromolecules can transform our understanding of biology and advance human health. Here, we map protein synthesis inside human cells in detail by combining ...Comprehensive in situ structures of macromolecules can transform our understanding of biology and advance human health. Here, we map protein synthesis inside human cells in detail by combining automated cryo-focused ion beam (FIB) milling and in situ single-particle cryo electron microscopy (cryo-EM). With this in situ cryo-EM approach, we resolved a 2.2 Å consensus structure of the human 80S ribosome and unveiled 23 functional states, nearly all better than 3 Å resolution. Compared to in vitro studies, we observed variations in ribosome structures, distinct environments of ion and polyamine binding, and associated proteins such as EDF1 and NACβ that are typically not enriched with purified ribosomes. We also detected additional peptide-related density features on the ribosome and visualized ribosome-ribosome interactions in helical polysomes. Finally, high-resolution structures from cells treated with homoharringtonine and cycloheximide revealed a distinct translational landscape and a spermidine that interacts with cycloheximide at the E site, one of the numerous polyamines that also bind native ribosomes. These results underscore the value of high-resolution in situ studies in the native environment. |
External links | Nat Commun / PubMed:41315256 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.19 - 3.91 Å |
| Structure data | EMDB-71329, PDB-9p6z: EMDB-71331, PDB-9p72: EMDB-71332, PDB-9p73: EMDB-71333, PDB-9p76: EMDB-71340, PDB-9p7f: EMDB-71341, PDB-9p7g: EMDB-71342, PDB-9p7h: EMDB-71343, PDB-9p7i: EMDB-71344, PDB-9p7j: EMDB-71345, PDB-9p7k: EMDB-71346, PDB-9p7l: EMDB-71348, PDB-9p7n: EMDB-71349, PDB-9p7o: EMDB-71355, PDB-9p7w: EMDB-71356, PDB-9p7x: EMDB-71357, PDB-9p7y: EMDB-71371, PDB-9p8b: EMDB-71377, PDB-9p8h: EMDB-71378, PDB-9p8i: EMDB-71411, PDB-9p9h: EMDB-71412, PDB-9p9i: EMDB-71413, PDB-9p9j: EMDB-71414, PDB-9p9k: EMDB-71435, PDB-9pa7: ![]() EMDB-71440: In situ human 80S ribosome (consensus map) ![]() EMDB-71441: In situ human 80S ribosome (focused on 60S) ![]() EMDB-71442: In situ human 80S ribosome (Focused on 40S body) ![]() EMDB-71443: In situ human 80S ribosome (Focused on 40S head) EMDB-71477, PDB-9pbe: EMDB-71696, PDB-9pkg: |
| Chemicals | ![]() ChemComp-MG: ![]() ChemComp-SPM: ![]() ChemComp-SPD: ![]() ChemComp-ZN: ![]() ChemComp-3HE: ![]() ChemComp-HMT: ![]() ChemComp-HOH: ![]() ChemComp-K: ![]() ChemComp-PUT: |
| Source |
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Keywords | RIBOSOME / in situ / Ribsome |
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homo sapiens (human)
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