9J9H

High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA

This is a non-PDB format compatible entry.

Summary for 9J9H

• Entry DOI: 10.2210/pdb9j9h/pdb
• EMDB information: 61272
• Descriptor: 28S ribosomal RNA, 60S ribosomal protein L28, 40S ribosomal protein S7, ... (82 entities in total)
• Functional Keywords: cryo-em, plasmodium falciparum, ribosome
• Biological source: Plasmodium falciparum 3D7; More
• Total number of polymer chains: 80
• Total formula weight: 3452215.36

Authors

Yan, X.F.,Gao, Y.G. (deposition date: 2024-08-22, release date: 2025-06-04, Last modification date: 2025-06-18)

Primary citation

Go, K.D.,Yan, X.F.,Wirjanata, G.,Ero, R.,Pazicky, S.,Dziekan, J.,Tjia, S.,Lescar, J.,Bozdech, Z.,Gao, Y.G.
Antimalarial drug artemisinin stabilizes PfRACK1 binding to the ribosome.
Structure, 2025

PubMed Abstract: Artemisinin and its derivatives represent the core agents in artemisinin combination therapies that are the current frontline treatment for P. falciparum and P. vivax malaria infections. Artemisinins are known to bind a wide array of proteins that disrupt the parasite's cellular physiology. Here, we show that artemisinins' cytotoxic activity involves structural alteration of key P. falciparum macromolecular complexes, including the ribosome, proteasome, and T-complex. The structural analysis revealed that, following artemisinin treatment, a larger population of Pf80S ribosomes binds PfRACK1. Unlike in most eukaryotes, PfRACK1 does not interact with the C-terminal tail of the r-protein uS3 that in Plasmodium is truncated. This likely suggests an evolved role of uS3 in facilitating RACK1-mediated translational regulation, which would potentially benefit the parasite under certain conditions. Stabilization of RACK1 ribosome interaction likely contributes to artemisinins' mode of action.

PubMed: 40480224
DOI: 10.1016/j.str.2025.05.008

Experimental method

ELECTRON MICROSCOPY (2.45 Å)