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TitleAntimalarial drug artemisinin stabilizes PfRACK1 binding to the ribosome.
Journal, issue, pagesStructure, Vol. 33, Issue 8, Page 1386-11397.e5, Year 2025
Publish dateAug 7, 2025
AuthorsKa Diam Go / Xin-Fu Yan / Grennady Wirjanata / Rya Ero / Samuel Pazicky / Jerzy Dziekan / Seth Tjia / Julien Lescar / Zbynek Bozdech / Yong-Gui Gao /
PubMed AbstractArtemisinin 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 ...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.
External linksStructure / PubMed:40480224
MethodsEM (single particle)
Resolution2.36 - 3.98 Å
Structure data

EMDB-61258: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to E-tRNA (consensus map)
Method: EM (single particle) / Resolution: 2.46 Å

EMDB-61259: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to E-tRNA (Large Ribosomal Subunit)
Method: EM (single particle) / Resolution: 2.4 Å

EMDB-61260: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to E-tRNA (Small Ribosomal Subunit Body)
Method: EM (single particle) / Resolution: 2.5 Å

EMDB-61261: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to E-tRNA (Small Ribosomal Subunit Head)
Method: EM (single particle) / Resolution: 2.6 Å

EMDB-61262: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA (consensus map)
Method: EM (single particle) / Resolution: 2.45 Å

EMDB-61263: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA (Large Ribosomal Subunit)
Method: EM (single particle) / Resolution: 2.36 Å

EMDB-61264: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA (Small Ribosomal Subunit Body)
Method: EM (single particle) / Resolution: 2.47 Å

EMDB-61265: High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA (Small Ribosomal Subunit Head)
Method: EM (single particle) / Resolution: 2.54 Å

61272

9j9h

EMDB-61272, PDB-9j9h:
High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA
Method: EM (single particle) / Resolution: 2.45 Å

61273

9j9i

EMDB-61273, PDB-9j9i:
High-resolution cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to E-tRNA
Method: EM (single particle) / Resolution: 2.46 Å

EMDB-61274: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to RACK1 and E-tRNA
Method: EM (single particle) / Resolution: 3.98 Å

EMDB-61275: Cryo-EM structure of the Plasmodium falciparum 80S ribosome bound to E-tRNA
Method: EM (single particle) / Resolution: 3.37 Å

Chemicals

ChemComp-MG:
Unknown entry

ChemComp-ZN:
Unknown entry

Source
  • plasmodium falciparum 3d7 (eukaryote)
KeywordsRIBOSOME / cryo-EM / Plasmodium falciparum

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