MassIVE MSV000092987

Partial Public PXD045740

Bifurcated malarial translation elongation cycle

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Description

Malaria parasites rely heavily on rapid, high fidelity protein synthesis to infect and replicate in human erythrocytes, making translation an attractive target for new anti-malarials. Unfortunately, our knowledge of the inner workings of translation inside the cell remain limited. Here, we have determined native structures of Pf80S ribosomes in multiple conformational and compositional states in situ, from cryoFIB-milled Plasmodium falciparum-infected human erythrocytes. We mapped the distributions of ribosomes among these states, defining the translational landscape across the morphologically distinct stages of the parasite asexual intraerythrocytic replication cycle. We then employed an interdisciplinary, multi-scaled approach to interrogate how inhibiting translation perturbs the distribution of ribosomes among these states and to elucidate the corresponding molecular, ultrastructural and cellular consequences. We observe a relatively uniform distribution of Pf80S ribosomes across the intermediate states of translation elongation in the cell, in contrast with what is observed in other organisms. Furthermore, we find two translation intermediates co-exist in trophozoite and schizont stage parasites that have not been seen together in other organisms thus far. Our work provides a deeper understanding of malarial protein synthesis, informing development of new therapies. [doi:10.25345/C5251FW46] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Pf80S ribosome ; Malaria ; in situ cryoET

Contact

Principal Investigators:
(in alphabetical order) 		Chi-Min Ho, Columbia University Irving Medical Center, United States
Submitting User: edoud
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Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

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