9p7o | pdb_00009p7o
In situ human AT-P-Z state ribosome
Structural highlights
DiseaseRS24_HUMAN Blackfan-Diamond disease. Diamond-Blackfan anemia 3 (DBA3) [MIM:610629: A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of developing leukemia. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent being craniofacial (Pierre-Robin syndrome and cleft palate), thumb and urogenital anomalies. Note=The disease is caused by mutations affecting the gene represented in this entry.[1] FunctionRS24_HUMAN Required for processing of pre-rRNA and maturation of 40S ribosomal subunits.[2] Publication Abstract from PubMedComprehensive 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 A consensus structure of the human 80S ribosome and unveiled 23 functional states, nearly all better than 3 A 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 NACbeta 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. Visualizing the translation landscape in human cells at high resolution.,Zheng W, Zhang Y, Wang J, Wang S, Chai P, Bailey EJ, Zhu C, Guo W, Devarkar SC, Wu S, Lin J, Zhang K, Liu J, Lomakin IB, Xiong Y Nat Commun. 2025 Nov 28;16(1):10757. doi: 10.1038/s41467-025-65795-9. PMID:41315256[3] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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