9P8H

In situ human A/P-P/E state 80S ribosome

This is a non-PDB format compatible entry.

Replaces:  9AZN

Summary for 9P8H

• Entry DOI: 10.2210/pdb9p8h/pdb
• EMDB information: 71377
• Descriptor: A/P site tRNA, 40S ribosomal protein S18, 40S ribosomal protein S19, ... (88 entities in total)
• Functional Keywords: in situ, ribosome
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 84
• Total formula weight: 3332608.41

Authors

Zheng, W.,Xiong, Y. (deposition date: 2025-06-23, release date: 2025-12-24)

Primary citation

Zheng, W.,Zhang, Y.,Wang, J.,Wang, S.,Chai, P.,Bailey, E.J.,Zhu, C.,Guo, W.,Devarkar, S.C.,Wu, S.,Lin, J.,Zhang, K.,Liu, J.,Lomakin, I.B.,Xiong, Y.
Visualizing the translation landscape in human cells at high resolution.
Nat Commun, 16:10757-10757, 2025

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 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.

PubMed: 41315256
DOI: 10.1038/s41467-025-65795-9

Experimental method

ELECTRON MICROSCOPY (2.98 Å)